Ribbon diagram of G-actin. ADP bound to actin's active site (multi color sticks near center of figure) as well as a complexed calcium dication (green sphere) are highlighted.[1]
Symbol Actin
Pfam PF00022
InterPro IPR004000
SCOP 2btf

Actin is a globular multi-functional protein that forms microfilaments. It is found in essentially all eukaryotic cells (the only known exception being nematode sperm), where it may be present at concentrations of over 100 μM. An actin protein's mass is roughly 42-kDa and it is the monomeric subunit of two types of filaments in cells: microfilaments, one of the three major components of the cytoskeleton, and thin filaments, part of the contractile apparatus in muscle cells. It can be present as either a free monomer called G-actin (globular) or as part of a linear polymer microfilament called F-actin (filamentous), both of which are essential for such important cellular functions as the mobility and contraction of cells during cell division.

Actin participates in many important cellular processes, including muscle contraction, cell cell signaling, and the establishment and maintenance of cell junctions and cell shape. Many of these processes are mediated by extensive and intimate interactions of actin with cellular membranes.[2] In vertebrates, three main groups of actin isoforms, alpha, beta, and gamma have been identified. The alpha actins, found in muscle tissues, are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton, and as mediators of internal cell motility. It is believed that the diverse range of structures formed by actin enabling it to fulfill such a large range of functions is regulated through the binding of tropomyosin along the filaments.[3]

A cell’s ability to dynamically form microfilaments provides the scaffolding that allows it to rapidly remodel itself in response to its environment or to the organism’s internal muscular contraction and cellular migration. It therefore plays an important role in embryogenesis, the healing of wounds and the invasivity of cancer cells. The evolutionary origin of actin can be traced to prokaryotic cells, which have equivalent proteins.[4] Actin homologs from prokaryotes and archea polymerize into different helical or linear filaments consisting of one or multiple strands. However the in-strand contacts and nucleotide binding sites are preserved in prokaryotes and in archea.[5] Lastly, actin plays an important role in the control of gene expression.

A large number of muscular diseases, variations in the size and function of the heart as well as deafness. The make-up of the cytoskeleton is also related to the pathogenicity of intracellular bacteria and viruses, particularly in the processes related to evading the actions of the immune system.[6]


  • History 1
  • Structure 2
    • G-Actin 2.1
    • F-Actin 2.2
    • Folding 2.3
    • ATPase’s catalytic mechanism 2.4
  • Genetics 3
  • Assembly dynamics 4
    • Nucleation and polymerization 4.1
    • Associated proteins 4.2
    • Chemical inhibitors 4.3
  • Functions and location 5
    • Cytoskeleton 5.1
      • Yeasts 5.1.1
      • Plants 5.1.2
    • Nuclear actin 5.2
    • Muscular contraction 5.3
      • Outline of a muscle contraction 5.3.1
      • Actin’s role in muscle contraction 5.3.2
    • Other biological processes 5.4
  • Molecular pathology 6
    • Pathology associated with ACTA1 6.1
    • In smooth muscle 6.2
    • In heart muscle 6.3
    • In cytoplasmatic actins 6.4
    • Other pathological mechanisms 6.5
  • Evolution 7
    • Equivalents in bacteria 7.1
  • Applications 8
  • See also 9
  • References 10
  • External links 11


Actin was first observed experimentally in 1887 by W.D. Halliburton, who extracted a protein from muscle that 'coagulated' preparations of myosin that he called "myosin-ferment".[7] However, Halliburton was unable to further refine his findings, and the discovery of actin is credited instead to Brunó Ferenc Straub, a young biochemist working in Albert Szent-Györgyi's laboratory at the Institute of Medical Chemistry at the University of Szeged, Hungary.

In 1942, Straub developed a novel technique for phosphate (which remain bound to the microfilament). Straub suggested that the transformation of ATP-bound actin to ADP-bound actin played a role in muscular contraction. In fact, this is true only in smooth muscle, and was not supported through experimentation until 2001.[9][10]

The amino acid sequencing of actin was completed by M. Elzinga and co-workers in 1973.[11] The crystal structure of G-actin was solved in 1990 by Kabsch and colleagues.[12] In the same year, a model for F-actin was proposed by Holmes and colleagues following experiments using co-crystallization with different proteins.[13] The procedure of co-crystallization with different proteins was used repeatedly during the following years, until in 2001 the isolated protein was crystallized along with ADP. However, there is still no high-resolution X-ray structure of F-actin. The crystallization of F-actin was possible due to the use of a rhodamine conjugate that impedes polymerization by blocking the amino acid cys-374.[1] Christine Oriol-Audit died in the same year that actin was first crystallized but she was the researcher that in 1977 first crystallized actin in the absence of Actin Binding Proteins (ABPs). However, the resulting crystals were too small for the available technology of the time.[14]

Although no high-resolution model of actin’s filamentous form currently exists, in 2008 Sawaya’s team were able to produce a more exact model of its structure based on multiple crystals of actin dimers that bind in different places.[15] This model has subsequently been further refined by Sawaya and Lorenz. Other approaches such as the use of cryo-electron microscopy and synchrotron radiation have recently allowed increasing resolution and better understanding of the nature of the interactions and conformational changes implicated in the formation of actin filaments.[16][17]


Its amino acid sequence is also one of the most highly conserved of the proteins as it has changed little over the course of evolution, differing by no more than 20% in species as diverse as algae and humans. It is therefore considered to have an optimised structure.[4] It has two distinguishing features: it is an enzyme that slowly hydrolizes ATP, the "universal energy currency" of biological processes. However, the ATP is required in order to maintain its structural integrity. Its efficient structure is formed by an almost unique folding process. In addition, it is able to carry out more interactions than any other protein, which allows it to perform a wider variety of functions than other proteins at almost every level of cellular life.[4] Myosin is an example of a protein that bonds with actin. Another example is villin, which can weave actin into bundles or cut the filaments depending on the concentration of calcium cations in the surrounding medium.[18]

Actin is one of the most abundant proteins in domains: in bacteria the actin homologue MreB has been identified, which is a protein that is capable of polymerizing into microfilaments; [4][17] and in archaea the homologue Ta0583 is even more similar to the eukaryotic actins.[21]

Cellular actin has two forms: monomeric globules called G-actin and polymeric filaments called F-actin (that is, as filaments made up of many G-actin monomers). F-actin can also be described as a microfilament. Two parallel F-actin strands must rotate 166 degrees to lie correctly on top of each other. This creates the double helix structure of the microfilaments found in the cytoskeleton. Microfilaments measure approximately 7 nm in diameter with the helix repeating every 37 nm. Each molecule of actin is bound to a molecule of adenosine triphosphate (ATP) or adenosine diphosphate (ADP) that is associated with a Mg2+ cation. The most commonly found forms of actin, compared to all the possible combinations, are ATP-G-Actin and ADP-F-actin.[22][23]


Scanning electron microscope images indicate that G-actin has a globular structure; however, X-ray crystallography shows that each of these globules consists of two lobes separated by a cleft. This structure represents the “ATPase fold”, which is a centre of enzymatic catalysis that binds ATP and Mg2+ and hydrolyzes the former to ADP plus phosphate. This fold is a conserved structural motif that is also found in other proteins that interact with triphosphate nucleotides such as hexokinase (an enzyme used in energy metabolism) or in Hsp70 proteins (a protein family that play an important part in protein folding).[24] G-actin is only functional when it contains either ADP or ATP in its cleft but the form that is bound to ATP predominates in cells when actin is present in its free state.[22]

Ribbon model of actin extracted from the striated muscle tissue of a rabbit after Graceffa and Domínguez, 2003. The four subdomains can be seen, as well as the N and C termini and the position of the ATP bond. The molecule is oriented using the usual convention of placing the - end (pointed end) in the upper part and the + end (barbed end) in the lower part.[1]

The X-ray crystallography model of actin that was produced by Kabsch from the striated muscle tissue of rabbits is the most commonly used in structural studies as it was the first to be purified. The G-actin crystallized by Kabsch is approximately 67 x 40 x 37 Å in size, has a molecular mass of 41,785 Da and an estimated isoelectric point of 4.8. Its net charge at pH = 7 is -7.[11][25]

Primary structure

Elzinga and co-workers first determined the complete peptide sequence for this type of actin in 1973, with later work by the same author adding further detail to the model. It contains 374 amino acid residues. Its N-terminus is highly acidic and starts with an acetyled aspartate in its amino group. While its C-terminus is alkaline and is formed by a phenylalanine preceded by a cysteine, which has a degree of functional importance. Both extremes are in close proximity within the I-subdomain. An anomalous Nτ-methylhistidine is located at position 73.[25]

Tertiary structure — domains

The tertiary structure is formed by two domains known as the large and the small, which are separated by a cleft centred around the location of the bond with ATP-ADP+Pi. Below this there is a deeper notch called a “groove”. In the native state, despite their names, both have a comparable depth.[11]

The normal convention in topological studies means that a protein is shown with the biggest domain on the left-hand side and the smallest domain on the right-hand side. In this position the smaller domain is in turn divided into two: subdomain I (lower position, residues 1-32, 70-144 and 338-374) and subdomain II (upper position, residues 33-69). The larger domain is also divided in two: subdomain III (lower, residues 145-180 and 270-337) and subdomain IV (higher, residues 181-269). The exposed areas of subdomains I and III are referred to as the “barbed” ends, while the exposed areas of domains II and IV are termed the “pointed" ends. This nomenclature refers to the fact that, due to the small mass of subdomain II actin is polar; the importance of this will be discussed below in the discussion on assembly dynamics. Some authors call the subdomains Ia, Ib, IIa and IIb, respectively.[26]

Other important structures

The most notable supersecondary structure is a five chain beta sheet that is composed of a β-meander and a β-α-β clockwise unit. It is present in both domains suggesting that the protein arose from gene duplication.[12]

  • The adenosine nucleotide binding site is located between two beta hairpin-shaped structures pertaining to the I and III domains. The residues that are involved are Asp11-Lys18 and Asp154-His161 respectively.
  • The divalent cation binding site is located just below that for the adenosine nucleotide. In vivo it is most often formed by Mg2+ or Ca2+ while in vitro it is formed by a chelating structure made up of Lys18 and two oxygens from the nucleotide’s α-and β-phosphates. This calcium is coordinated with six water molecules that are retained by the amino acids Asp11, Asp154, and Gln137. They form a complex with the nucleotide that restricts the movements of the so-called "hinge" region, located between residues 137 and 144. This maintains the native form of the protein until its withdrawal denatures the actin monomer. This region is also important because it determines whether the protein’s cleft is in the "open" or "closed" conformation.[1][26]
  • It is highly likely that there are at least three other centres with a lesser affinity (intermediate) and still others with a low affinity for divalent cations. It has been suggested that these centres may play a role in the polymerization of actin by acting during the activation stage.[26]
  • There is a structure in subdomain 2 that is called the “D-loop” because it binds with DNase I, it is located between the His40 and Gly48 residues. It has the appearance of a disorderly element in the majority of crystals, but it looks like a β-sheet when it is complexed with DNase I. Domínguez “et al.” suggest that the key event in polymerization is probably the propagation of a conformational change from the centre of the bond with the nucleotide to this domain, which changes from a loop to a spiral. However, this theory has been refuted by other studies.[1][27]


F-actin; surface representation of a repetition of 13 subunits based on Ken Holmes' actin filament model.[13]

The classical description of F-actin states that it has a filamentous structure that can be considered to be a single stranded levorotatory helix with a rotation of 166° around the helical axis and an axial translation of 27.5 Å, or a single stranded dextrorotatory helix with a cross over spacing of 350-380 Å, with each actin surrounded by four more.[28] The symmetry of the actin polymer at 2.17 subunits per turn of a helix is incompatible with the formation of crystals, which is only possible with a symmetry of exactly 2, 3, 4 or 6 subunits per turn. Therefore, models have to be constructed that explain these anomalies using data from electron microscopy, cryo-electron microscopy, crystallization of dimers in different positions and diffraction of X-rays.[17] It should be pointed out that it is not correct to talk of a “structure” for a molecule as dynamic as the actin filament. In reality we talk of distinct structural states, in these the measurement of axial translation remains constant at 27.5 Å while the subunit rotation data shows considerable variability, with displacements of up to 10% from its optimum position commonly seen. Some proteins, such as cofilin appear to increase the angle of turn, but again this could be interpreted as the establishment of different "structural states". These could be important in the polymerization process.[29]

There is less agreement regarding measurements of the turn radius and filament thickness: while the first models assigned a longitude of 25 Å, current X-ray diffraction data, backed up by cryo-electron microscopy suggests a longitude of 23.7 Å. These studies have shown the precise contact points between monomers. Some are formed with units of the same chain, between the "barbed" end on one monomer and the "pointed" end of the next one. While the monomers in adjacent chains make lateral contact through projections from subdomain IV, with the most important projections being those formed by the C-terminus and the hydrophobic link formed by three bodies involving residues 39-42, 201-203 and 286. This model suggests that a filament is formed by monomers in a "sheet" formation, in which the subdomains turn about themselves, this form is also found in the bacterial actin homologue MreB.[17]

The F-actin polymer is considered to have structural polarity due to the fact that all the microfilament’s subunits point towards the same end. This gives rise to a naming convention: the end that possesses an actin subunit that has its ATP binding site exposed is called the "(-) end", while the opposite end where the cleft is directed at a different adjacent monomer is called the "(+) end".[20] The terms "pointed" and "barbed" referring to the two ends of the microfilaments derive from their appearance under transmission electron microscopy when samples are examined following a preparation technique called "decoration". This method consists of the addition of myosin S1 fragments to tissue that has been fixed with tannic acid. This myosin forms polar bonds with actin monomers, giving rise to a configuration that looks like arrows with feather fletchings along its shaft, where the shaft is the actin and the fletchings are the myosin. Following this logic, the end of the microfilament that does not have any protruding myosin is called the point of the arrow (- end) and the other end is called the barbed end (+ end).[30] A S1 fragment is composed of the head and neck domains of myosin II. Under physiological conditions, G-actin (the monomer form) is transformed to F-actin (the polymer form) by ATP, where the role of ATP is essential.[31]

The helical F-actin filament found in muscles also contains a tropomyosin molecule, which is a 40 nanometre long protein that is wrapped around the F-actin helix. During the resting phase the tropomyosin covers the actin’s active sites so that the actin-myosin interaction cannot take place and produce muscular contraction. There are other protein molecules bound to the tropomyosin thread, these are the troponins that have three polymers: troponin I, troponin T and troponin C.[32]


Ribbon model obtained using the PyMOL programme on crystallographs of the prefoldin proteins found in the archaean Pyrococcus horikoshii. The six supersecondary structures are present in a coiled helix “hanging” from the central beta barrels. These are often compared in the literature to the tentacles of a jellyfish. As far as is visible using electron microscopy, eukariotic prefoldin has a similar structure.[33]

Actin can spontaneously acquire a large part of its tertiary structure.[34] However, the way it acquires its fully functional form from its newly synthesized native form is special and almost unique in protein chemistry. The reason for this special route could be the need to avoid the presence of incorrectly folded actin monomers, which could be toxic as they can act as inefficient polymerization terminators. Nevertheless, it is key to establishing the stability of the cytoskeleton, and additionally, it is an essential process for coordinating the cell cycle.[35][36]

CCT is required in order to ensure that folding takes place correctly. CCT is a group II cytosolic molecular chaperone (or chaperonin, a protein that assists in the folding of other macromolecular structures). CCT is formed of a double ring of eight different subunits (hetero-octameric) and it differs from other molecular chaperones, particularly from its homologue GroEL which is found in the Archaea, as it does not require a co-chaperone to act as a lid over the central catalytic cavity. Substrates bind to CCT through specific domains. It was initially thought that it only bound with actin and tubulin, although recent immunoprecipitation studies have shown that it interacts with a large number of polypeptides, which possibly function as substrates. It acts through ATP-dependent conformational changes that on occasion require several rounds of liberation and catalysis in order to complete a reaction.[37]

In order to successfully complete their folding, both actin and tubulin need to interact with another protein called prefoldin, which is a heterohexameric complex (formed by six distinct subunits), in an interaction that is so specific that the molecules have coevolved. Actin complexes with prefoldin while it is still being formed, when it is approximately 145 amino acids long, specifically those at the N-terminal.[38]

Different recognition sub-units are used for actin or tubulin although there is some overlap. In actin the subunits that bind with prefoldin are probably PFD3 and PFD4, which bind in two places one between residues 60-79 and the other between residues 170-198. The actin is recognized, loaded and delivered to the cytosolic chaperonin (CCT) in an open conformation by the inner end of prefoldin’s "tentacles” (see the image and note).[34] The contact when actin is delivered is so brief that a tertiary complex is not formed, immediately freeing the prefoldin.[33]

Ribbon model of the apical γ-domain of the chaperonin CCT.

The CCT then causes actin's sequential folding by forming bonds with its subunits rather than simply enclosing it in its cavity.[39] This is why it possesses specific recognition areas in its apical β-domain. The first stage in the folding consists of the recognition of residues 245-249. Next, other determinants establish contact.[40] Both actin and tubulin bind to CCT in open conformations in the absence of ATP. In actin’s case, two subunits are bound during each conformational change, whereas for tubulin binding takes place with four subunits. Actin has specific binding sequences, which interact with the δ and β-CCT subunits or with δ-CCT and ε-CCT. After AMP-PNP is bound to CCT the substrates move within the chaperonin’s cavity. It also seems that in the case of actin, the CAP protein is required as a possible cofactor in actin's final folding states.[36]

The exact manner by which this process is regulated is still not fully understood, but it is known that the protein PhLP3 (a protein similar to phosducin) inhibits its activity through the formation of a tertiary complex.[37]

ATPase’s catalytic mechanism

Actin is an ATPase, which means that it is an enzyme that hydrolyzes ATP. This group of enzymes is characterised by their slow reaction rates. It is known that this ATPase is “active”, that is, its speed increases by some 40,000 times when the actin forms part of a filament.[29] A reference value for this rate of hydrolysis under ideal conditions is around 0.3 s−1. Then, the Pi remains bound to the actin next to the ADP for a long time, until it is liberated next to the end of the filament.[41]

The exact molecular details of the catalytic mechanism are still not fully understood. Although there is much debate on this issue, it seems certain that a "closed" conformation is required for the hydrolysis of ATP, and it is thought that the residues that are involved in the process move to the appropriate distance.[29] The glutamic acid Glu137 is one of the key residues, which is located in subdomain 1. Its function is to bind the water molecule that produces a nucleophilic attack on the ATP’s γ-phosphate bond, while the nucleotide is strongly bound to subdomains 3 and 4. The slowness of the catalytic process is due to the large distance and skewed position of the water molecule in relation to the reactant. It is highly likely that the conformational change produced by the rotation of the domains between actin’s G and F forms moves the Glu137 closer allowing its hydrolysis. This model suggests that the polymerization and ATPase’s function would be decoupled straight away.[17]


Principal interactions of structural proteins are at cadherin-based adherens junction. Actin filaments are linked to α-actinin and to the membrane through vinculin. The head domain of vinculin associates to E-cadherin via α-catenin, β-catenin, and γ-catenin. The tail domain of vinculin binds to membrane lipids and to actin filaments.

Actin has been one of the most highly conserved proteins throughout evolution because it interacts with a large number of other proteins. It has 80.2% sequence conservation at the gene level between Homo sapiens and Saccharomyces cerevisiae (a species of yeast), and 95% conservation of the primary structure of the protein product.[4]

Although most yeasts have only a single actin gene, higher eukaryotes, in general, express several isoforms of actin encoded by a family of related genes. Mammals have at least six actin isoforms coded by separate genes,[42] which are divided into three classes (alpha, beta and gamma) according to their isoelectric points. In general, alpha actins are found in muscle (α-skeletal, α-aortic smooth, α-cardiac, and γ2-enteric smooth), whereas beta and gamma isoforms are prominent in non-muscle cells (β- and γ1-cytoplasmic). Although the amino acid sequences and in vitro properties of the isoforms are highly similar, these isoforms cannot completely substitute for one another in vivo.[43]

The typical actin gene has an approximately 100-nucleotide 5' UTR, a 1200-nucleotide translated region, and a 200-nucleotide 3' UTR. The majority of actin genes are interrupted by introns, with up to six introns in any of 19 well-characterised locations. The high conservation of the family makes actin the favoured model for studies comparing the introns-early and introns-late models of intron evolution.

All non-spherical prokaryotes appear to possess genes such as MreB, which encode homologues of actin; these genes are required for the cell's shape to be maintained. The plasmid-derived gene ParM encodes an actin-like protein whose polymerized form is dynamically unstable, and appears to partition the plasmid DNA into its daughter cells during cell division by a mechanism analogous to that employed by microtubules in eukaryotic mitosis.[44] Actin is found in both smooth and rough endoplasmic reticulums.

Assembly dynamics

Nucleation and polymerization

Thin filament formation showing the polymerization mechanism for converting G-actin to F-actin; note the hydrolysis of the ATP.

Actin polymerization and depolymerization is necessary in chemotaxis and cytokinesis. Nucleating factors are necessary to stimulate actin polymerization. One such nucleating factor is the Arp2/3 complex, which mimics a G-actin dimer in order to stimulate the nucleation (or formation of the first trimer) of monomeric G-actin. The Arp2/3 complex binds to actin filaments at 70 degrees to form new actin branches off existing actin filaments. Also, actin filaments themselves bind ATP, and hydrolysis of this ATP stimulates destabilization of the polymer.

The growth of actin filaments can be regulated by thymosin and profilin. Thymosin binds to G-actin to buffer the polymerizing process, while profilin binds to G-actin to exchange ADP for ATP, promoting the monomeric addition to the barbed, plus end of F-actin filaments.

F-actin is both strong and dynamic. Unlike other polymers, such as DNA, whose constituent elements are bound together with covalent bonds, the monomers of actin filaments are assembled by weaker bonds. The lateral bonds with neighbouring monomers resolve this anomaly, which in theory should weaken the structure as they can be broken by thermal agitation. In addition, the weak bonds give the advantage that the filament ends can easily release or incorporate monomers. This means that the filaments can be rapidly remodelled and can change cellular structure in response to an environmental stimulus. Which, along with the biochemical mechanism by which it is brought about is known as the "assembly dynamic".[6]

In vitro studies

Studies focusing on the accumulation and loss of subunits by microfilaments are carried out in vitro (that is, in the laboratory and not on cellular systems) as the polymerization of the resulting actin gives rise to the same F-actin as produced in vivo. The in vivo process is controlled by a multitude of proteins in order to make it responsive to cellular demands, this makes it difficult to observe its basic conditions.[45]

In vitro production takes place in a sequential manner: first, there is the "activation phase", when the bonding and exchange of divalent cations occurs in specific places on the G-actin, which is bound to ATP. This produces a conformational change, sometimes called G*-actin or F-actin monomer as it is very similar to the units that are located on the filament.[26] This prepares it for the "nucleation phase", in which the G-actin gives rise to small unstable fragments of F-actin that are able to polymerize. Unstable dimers and trimers are initially formed. The "elongation phase" begins when there are a sufficiently large number of these short polymers. In this phase the filament forms and rapidly grows through the reversible addition of new monomers at both extremes.[46] Finally, a "stationary equilibrium" is achieved where the G-actin monomers are exchanged at both ends of the microfilament without any change to its total length.[18] In this last phase the "critical concentration Cc" is defined as the ratio between the assembly constant and the dissociation constant for G-actin, where the dynamic for the addition and elimination of dimers and trimers does not produce a change in the microfilament's length. Under normal “in vitro” conditions Cc is 0.1 μM,[47] which means that at higher values polymerization occurs and at lower values depolymerization occurs.[48]

Role of ATP hydrolysis

As indicated above, although actin hydrolyzes ATP, everything points to the fact that ATP is not required for actin to be assembled, given that, on one hand, the hydrolysis mainly takes place inside the filament, and on the other hand the ADP could also instigate polymerization. This poses the question of understanding which thermodynamically unfavourable process requires such a prodigious expenditure of energy. The so-called “actin cycle”, which couples ATP hydrolysis to actin polymerization, consists of the preferential addition of G-actin-ATP monomers to a filament’s barbed end, and the simultaneous disassembly of F-actin-ADP monomers at the pointed end where the ADP is subsequently changed into ATP, thereby closing the cycle, this aspect of actin filament formation is known as “treadmilling”.

ATP is hydrolysed relatively rapidly just after the addition of a G-actin monomer to the filament. There are two hypotheses regarding how this occurs; the stochastic, which suggests that hydrolysis randomly occurs in a manner that is in some way influenced by the neighbouring molecules; and the vectoral, which suggests that hydrolysis only occurs adjacent to other molecules whose ATP has already been hydrolysed. In either case, the resulting Pi is not released, it remains for some time noncovalently bound to actin’s ADP, in this way there are three species of actin in a filament: ATP-Actin, ADP+Pi-Actin and ADP-Actin.[41][49] The amount of each one of these species present in a filament depends on its length and state: as elongation commences the filament has an approximately equal amount of actin monomers bound with ATP and ADP+Pi and a small amount of ADP-Actin at the (-) end. As the stationary state is reached the situation reverses, with ADP present along the majority of the filament and only the area nearest the (+) end containing ADP+Pi and with ATP only present at the tip.[50]

If we compare the filaments that only contain ADP-Actin with those that include ATP, in the former the critical constants are similar at both ends, while Cc for the other two nucleotides is different: At the (+) end Cc+=0.1 μM, while at the (-) end Cc=0.8 μM, which gives rise to the following situations:[20]

  • For G-actin-ATP concentrations less than Cc+ no elongation of the filament occurs.
  • For G-actin-ATP concentrations less than Cc but greater than Cc+ elongation occurs at the (+) end.
  • For G-actin-ATP concentrations greater than Cc the microfilament grows at both ends.

It is therefore possible to deduce that the energy produced by hydrolysis is used to create a true “stationary state”, that is a flux, instead of a simple equilibrium, one that is dynamic, polar and attached to the filament. This justifies the expenditure of energy as it promotes essential biological functions.[41] In addition, the configuration of the different monomer types is detected by actin binding proteins, which also control this dynamism, as will be described in the following section.

Microfilament formation by treadmilling has been found to be atypical in stereocilia. In this case the control of the structure's size is totally apical and it is controlled in some way by gene expression, that is, by the total quantity of protein monomer synthesized in any given moment.[51]

Associated proteins

An actin (green) - profilin (blue) complex.[52] The profilin shown belongs to group II, normally present in the kidneys and the brain.

The actin cytoskeleton

  • genes are available. For example, if the α-actinin or gelation factor gene has been removed in Dictyostelium individuals do not show an anomalous phenotype possibly due to the fact that each of the proteins can perform the function of the other. However, the development of double mutations that lack both gene types is affected.[90]
  • Candida albicans
Diagram of a zonula occludens or tight junction, a structure that joins the epithelium of two cells. Actin is one of the anchoring elements shown in green.
  • Cytokinesis. Cell division in animal cells and yeasts normally involves the separation of the parent cell into two daughter cells through the constriction of the central circumference. This process involves a constricting ring composed of actin, myosin, and α-actinin.[83] In the "fission yeast” Schizosaccharomyces pombe, actin is actively formed in the constricting ring with the participation of Arp3, the formin Cdc12, profilin, and WASp, along with preformed microfilaments. Once the ring has been constructed the structure is maintained by a continual assembly and disassembly that, aided by the Arp2/3 complex and formins, is key to one of the central processes of cytokinesis.[84] The totality of the contractile ring, the spindle apparatus, microtubules and the dense peripheral material is called the "Fleming body» or "intermediate body».[73]
  • stress fibers; this is activated by the MAP kinase pathway.[88]

The traditional image of actin’s function relates it to the maintenance of the cytoskeleton and, therefore, the organization and movement of organelles, as well as the determination of a cell’s shape.[73] However, actin has a wider role in eukaryotic cell physiology, in addition to similar functions in prokaryotes.

Fluorescence imaging of actin dynamics during the first embryonic cell division of C. elegans. First, actin filaments assemble in the upper part of the cell, thus contributing to asymmetric cell division. Then, at 10 s, formation of the contractile actin ring can be observed.

Other biological processes

  1. Depolarization of the sarcolemma and transmission of an action potential through the T-tubules.
  2. Opening of the sarcoplasmic reticulum’s Ca2+ channels.
  3. Increase in cytosolic Ca2+ concentrations and the interaction of these cations with troponin causing a conformational change in its structure. This in turn alters the structure of tropomyosin, which covers actin’s active site, allowing the formation of myosin-actin cross-links (the latter being present as thin filaments).[32]
  4. Movement of myosin heads over the thin filaments, this can either involve ATP or be independent of ATP. The former mechanism, mediated by ATPase activity in the myosin heads, causes the movement of the actin filaments towards the Z-disc.
  5. Ca2+ capture by the sarcoplasmic reticulum, causing a new conformational change in tropomyosin that inhibits the actin-myosin interaction.[82]

Both actin and myosin are involved in muscle contraction and relaxation and they make up 90% of muscle protein.[82] The overall process is initiated by an external signal, typically through an action potential stimulating the muscle, which contains specialized cells whose interiors are rich in actin and myosin filaments. The contraction-relaxation cycle comprises the following steps:[71]

The helical F-actin filament found in muscles also contains a tropomyosin molecule, a 40-nanometre protein that is wrapped around the F-actin helix. During the resting phase the tropomyosin covers the actin’s active sites so that the actin-myosin interaction cannot take place and produce muscular contraction (the interaction gives rise to a movement between the two proteins that, because it is repeated many times, produces a contraction). There are other protein molecules bound to the tropomyosin thread, these include the troponins that have three polymers: troponin I, troponin T, and troponin C.[32] Tropomyosin’s regulatory function depends on its interaction with troponin in the presence of Ca2+ ions.[81]

Actin’s role in muscle contraction

In contractile bundles, the actin-bundling protein alpha-actinin separates each thin filament by ~35 nm. This increase in distance allows thick filaments to fit in between and interact, enabling deformation or contraction. In deformation, one end of myosin is bound to the plasma membrane, while the other end "walks" toward the plus end of the actin filament. This pulls the membrane into a different shape relative to the cell cortex. For contraction, the myosin molecule is usually bound to two separate filaments and both ends simultaneously "walk" toward their filament's plus end, sliding the actin filaments closer to each other. This results in the shortening, or contraction, of the actin bundle (but not the filament). This mechanism is responsible for muscle contraction and cytokinesis, the division of one cell into two.

In muscle, actin is the major component of thin filaments, which, together with the motor protein myosin (which forms thick filaments), are arranged into actomyosin myofibrils. These fibrils comprise the mechanism of muscle contraction. Using the hydrolysis of ATP for energy, myosin heads undergo a cycle during which they attach to thin filaments, exert a tension, and then, depending on the load, perform a power stroke that causes the thin filaments to slide past, shortening the muscle.

Outline of a muscle contraction

The structure of a sarcomere, the basic morphological and functional unit of the skeletal muscles that contains actin.

Muscular contraction

Actin is essential for transcription from RNA polymerases Pol I, Pol II and Pol III. In Pol I transcription, actin and myosin (MYO1C, which binds DNA) act as a molecular motor. For Pol II transcription, β-actin is needed for the formation of the preinitiation complex. Pol III contains β-actin as a subunit. Actin can also be a component of chromatin remodelling complexes as well as pre-mRNP particles (that is, precursor messenger RNA bundled in proteins), and is involved in nuclear export of RNAs and proteins.[80]

Nuclear actin

The most notable proteins associated with the actin cytoskeleton in plants include:[78] stress.

Even though the majority of plant cells have a cell division as well as the elongation and differentiation of the cell.[78]

Structure of the C-terminal subdomain of villin, a protein capable of splitting microfilaments.[77]

[76]. There is a concentration of the network around the nucleus that is connected via spokes to the cellular cortex, this network is highly dynamic, with a continuous polymerization and vitro analysed. Actin networks are distributed throughout the cytoplasm of cells that have been cultivated tissue The majority of these proteins were jointly expressed in the [4] Plant


[75]; Aip1, a cofilin cofactor that promotes the disassembly of microfilaments; Srv2/CAP, a process regulator related to COF1 Yeasts contain three main elements that are associated with actin: patches, cables and rings that, despite being present for long, are subject to a dynamic equilibrium due to continual polymerization and depolymerization. They possess a number of accessory proteins including ADF/cofilin, which has a molecular weight of 16kDa and is coded for by a single gene, called

Actin’s cytoskeleton is key to the processes of endocytosis, cytokinesis, determination of cell polarity and morphogenesis in yeasts. In addition to relying on actin these processes involve 20 or 30 associated proteins, which all have a high degree of evolutionary conservation, along with many signalling molecules. Together these elements allow a spatially and temporally modulated assembly that defines a cell’s response to both internal and external stimuli.[75]


  • Microfilament bundles. These extremely long microfilaments are located in networks and, in association with contractile proteins such as non-muscular myosin, they are involved in the movement of substances at an intracellular level.
  • Periodic actin rings. A periodic structure constructed of evenly spaced actin rings is recently found to specifically exist in axons (not dendrites).[74] In this structure, the actin rings, together with spectrin tetramers that link the neighboring actin rings, form a cohesive cytoskeleton that supports the axon membrane. The structure periodicity may also regulate the sodium ion channels in axons.
A merged stack of confocal images showing actin filaments within a cell. The image has been colour coded in the z axis to show in a 2D image which heights filaments can be found at within cells.
  • Microfilament networks. receptor cells that relay signals to the outside of a cell.

Microfilaments are involved in the movement of all mobile cells, including non-muscular types, and drugs that disrupt F-actin organization (such as the cytochalasins) affect the activity of these cells. Actin comprises 2% of the total amount of proteins in hepatocytes, 10% in fibroblasts, 15% in amoebas and up to 50-80% in activated platelets.[72] There are a number of different types of actin with slightly different structures and functions. This means that α-actin is found exclusively in muscle fibres, while types β and γ are found in other cells. In addition, as the latter types have a high turnover rate the majority of them are found outside permanent structures. This means that the microfilaments found in cells other than muscle cells are present in two forms:[73]

Fluorescence micrograph showing F-actin (in green) in rat fibroblasts.


The actin protein is found in both the cytoplasm and the cell nucleus.[69] Its location is regulated by cell membrane signal transduction pathways that integrate the stimuli that a cell receives stimulating the restructuring of the actin networks in response. In Dictyostelium, phospholipase D has been found to intervene in inositol phosphate pathways.[70] Actin filaments are particularly stable and abundant in muscle fibres. Within the sarcomere (the basic morphological and physiological unit of muscle fibres) actin is present in both the I and A bands; myosin is also present in the latter.[71]

  • Various types of actin networks (made of actin filaments) give mechanical support to cells, and provide trafficking routes through the cytoplasm to aid signal transduction
  • Rapid assembly and disassembly of actin network enables cells to migrate (Cell migration).
  • In metazoan muscle cells, to be the scaffold on which myosin proteins generate force to support muscle contraction
  • In non-muscle cells, to be a track for cargo transport myosins (nonconventional myosins) such as myosin V and VI. Nonconventional myosins use ATP hydrolysis to transport cargo, such as vesicles and organelles, in a directed fashion much faster than diffusion. Myosin V walks towards the barbed end of actin filaments, while myosin VI walks toward the pointed end. Most actin filaments are arranged with the barbed end toward the cellular membrane and the pointed end toward the cellular interior. This arrangement allows myosin V to be an effective motor for the export of cargos, and myosin VI to be an effective motor for import.

Actin forms filaments ('F-actin' or microfilaments) that are essential elements of the eukaryotic cytoskeleton, able to undergo very fast polymerization and depolymerization dynamics. In most cells actin filaments form larger-scale networks which are essential for many key functions in cells:[68]

Functions and location

  • Latrunculin is a toxin produced by sponges, it binds to G-actin preventing it from binding with microfilaments.[65]
  • Cytocalasin D, is an alkaloid produced by fungi, that binds to the (+) end of F-actin preventing the addition of new monomers.[66] Cytocalasin D has been found to disrupt actin’s dynamics, activating protein p53 in animals.[67]
  • Phalloidin, is a toxin that has been isolated from the death cap mushroom Amanita phalloides. It binds to the interface between adjacent actin monomers in the F-actin polymer, preventing its depolymerization.[66]

There are a number of toxins that interfere with actin’s dynamics, either by preventing it from polymerizing (latrunculin and cytochalasin D) or by stabilizing it (phalloidin):

Chemical structure of phalloidin.

Chemical inhibitors

[64] (the reconnection of two branching structures that had previously been joined, such as in blood vessels).anastomosis structures and also in dendritic in the polymerization of G-actin and F-actin. This complex is also required in more complicated processes such as in establishing nucleation agents that is clearly related to their biological function: two of the subunits, "ARP2» and "ARP3», have a structure similar to that of actin monomers. This homology allows both units to act as topology It is composed of seven subunits, some of which possess a [63] The

Atomic structure of Arp2/3.[62] Each colour corresponds to a subunit: Arp3, orange; Arp2, sea blue (subunits 1 and 2 are not shown); p40, green; p34, light blue; p20, dark blue; p21, magenta; p16, yellow.

Other proteins that bind with actin cover the ends of F-actin in order to stabilize them, but they are unable to break them. Examples of this type of protein are CapZ (that binds the (+) ends depending on a cell’s levels of Ca2+/calmodulin. These levels depend on the cell’s internal and external signals and are involved in the regulation of its biological functions).[60] Another example is tropomodulin (that binds to the (-) end). Tropomodulin basically acts to stabilize the F-actin present in the myofibrils present in muscle sarcomeres, which are structures characterized by their great stability.[61]

Other proteins that bind to actin regulate the length of the microfilaments by cutting them, which gives rise to new active ends for polymerization. For example, if a microfilament with two ends is cut twice, there will be three new microfilaments with six ends. This new situation favors the dynamics of assembly and disassembly. The most notable of these proteins are gelsolin and cofilin. These proteins first achieve a cut by binding to an actin monomer located in the polymer they then change the actin monomer’s conformation while remaining bound to the newly generated (+) end. This has the effect of impeding the addition or exchange of new G-actin subunits. Depolymerization is encouraged as the (-) ends are not linked to any other molecule.[59]

The protein gelsolin, which is a key regulator in the assembly and disassembly of actin. It has six subdomains, S1-S6, each of which is composed of a five-stranded β-sheet flanked by two α-helices, one positioned perpendicular to the strands and the other in a parallel position. Both the N-terminal end, (S1-S3), and the C-terminal end, (S4-S6), form an extended β-sheet.[57] [58]
  • Thymosin β-4 is a 5 kDa protein that can bind with G-actin-ATP in a 1:1 stoichiometry; which means that one unit of thymosin β-4 binds to one unit of G-actin. Its role is to impede the incorporation of the monomers into the growing polymer.[54]
  • Profilin, is a cytosolic protein with a molecular weight of 15 kDa, which also binds with G-actin-ATP or -ADP with a stoichiometry of 1:1, but it has a different function as it facilitates the replacement of ADP nucleotides by ATP. It is also implicated in other cellular functions, such as the binding of proline repetitions in other proteins or of lipids that act as secondary messengers.[55][56]

[20] For example, G-actin sequestering elements exist that impede its incorporation into microfilaments. There are also proteins that stimulate its polymerization or that give complexity to the synthesizing networks.[53].protein-protein interactions The diversity of these proteins is such that actin is thought to be the protein that takes part in the greatest number of [18].[92] In addition, proteins that are similar to actin play a regulatory role during spermatogenesis in mice[93] and, in yeasts, actin-like proteins are thought to play a role in the regulation of gene expression.[94] In fact, actin is capable of acting as a transcription initiator when it reacts with a type of nuclear myosin that interacts with RNA polymerases and other enzymes involved in the transcription process.[69]

  • ear . The main characteristic of these structures is that their length can be modified.[95] The molecular architecture of the stereocilia includes a paracrystalline actin core in dynamic equilibrium with the monomers present in the adjacent cytosol. Type VI and VIIa myosins are present throughout this core, while myosin XVa is present in its extremities in quantities that are proportional to the length of the stereocilia.[96]
  • Molecular pathology

    The majority of mammals possess six different actin genes. Of these, two code for the cytoskeleton (ACTB and ACTG1) while the other four are involved in skeletal striated muscle (ACTA1), smooth muscle tissue (ACTA2), intestinal muscles (ACTG2) and cardiac muscle (ACTC1). The actin in the cytoskeleton is involved in the pathogenic mechanisms of many infectious agents, including HIV. The vast majority of the mutations that affect actin are point mutations that have a dominant effect, with the exception of six mutations involved in nemaline myopathy. This is because in many cases the mutant of the actin monomer acts as a “cap” by preventing the elongation of F-actin.[26]

    Pathology associated with ACTA1

    ACTA1 is the gene that codes for the α-isoform of actin that is predominant in human skeletal striated muscles, although it is also expressed in heart muscle and in the thyroid gland.[97] Its DNA sequence consists of seven exons that produce five known transcripts.[98] The majority of these consist of point mutations causing substitution of amino acids. The mutations are in many cases associated with a phenotype that determines the severity and the course of the affliction.[26][98]

    Giant nemaline rods produced by the transfection of a DNA sequence of ACTA1, which is the carrier of a mutation responsible for nemaline myopathy.[99]

    The mutation alters the structure and function of skeletal muscles producing one of three forms of myopathy: type 3 nemaline myopathy, congenital myopathy with an excess of thin myofilaments (CM) and Congenital myopathy with fibre type disproportion (CMFTD). Mutations have also been found that produce “core” myopathies).[100] Although their phenotypes are similar, in addition to typical nemaline myopathy some specialists distinguish another type of myopathy called actinic nemaline myopathy. In the former, clumps of actin form instead of the typical rods. It is important to state that a patient can show more than one of these phenotypes in a biopsy.[101] The most common symptoms consist of a typical facial morphology (myopathic faces), muscular weakness, a delay in motor development and respiratory difficulties. The course of the illness, its gravity and the age at which it appears are all variable and overlapping forms of myopathy are also found. A symptom of nemalinic myopathy is that “Nemaline rods” appear in differing places in Type 1 muscle fibres. These rods are non-pathognomonic structures that have a similar composition to the Z disks found in the sarcomere.[102]

    The pathogenesis of this myopathy is very varied. Many mutations occur in the region of actin’s indentation near to its nucleotide binding sites, while others occur in Domain 2, or in the areas where interaction occurs with associated proteins. This goes some way to explain the great variety of clumps that form in these cases, such as Nemaline or Intranuclear Bodies or Zebra Bodies.[26] Changes in actin’s folding occur in nemaline myopathy as well as changes in its aggregation and there are also changes in the expression of other associated proteins. In some variants where intranuclear bodies are found the changes in the folding masks the nucleus’s protein exportation signal so that the accumulation of actin's mutated form occurs in the cell nucleus.[103] On the other hand it appears that mutations to ACTA1 that give rise to a CFTDM have a greater effect on sarcomeric function than on its structure.[104] Recent investigations have tried to understand this apparent paradox, which suggests there is no clear correlation between the number of rods and muscular weakness. It appears that some mutations are able to induce a greater apoptosis rate in type II muscular fibres.[35]

    Position of seven mutations relevant to the various actinopathies related to ACTA1.[99]

    In smooth muscle

    There are two isoforms that code for actins in the smooth muscle tissue:

    ACTG2 codes for the largest actin isoform, which has nine exons, one of which, the one located at the 5' end, is not translated.[105] It is an γ-actin that is expressed in the enteric smooth muscle. No mutations to this gene have been found that correspond to pathologies, although microarrays have shown that this protein is more often expressed in cases that are resistant to chemotherapy using cisplatin.[106]

    hyperplasia as well as stenosis of the aorta’s vasa vasorum.[107] The number of afflictions that the gene is implicated in is increasing. It has been related to Moyamoya disease and it seems likely that certain mutations in heterozygosis could confer a predisposition to many vascular pathologies, such as thoracic aortic aneurysm and ischaemic heart disease.[108] The α-actin found in smooth muscles is also an interesting marker for evaluating the progress of liver cirrhosis.[109]

    In heart muscle

    The ACTC1 gene codes for the α-actin isoform present in heart muscle. It was first sequenced by Hamada and co-workers in 1982, when it was found that it is interrupted by five introns.[110] It was the first of the six genes where alleles were found that were implicated in pathological processes.[111]

    Crossection of a rat heart that is showing signs of dilated cardiomyopathy.[112]

    A number of structural disorders associated with point mutations of this gene have been described that cause malfunctioning of the heart, such as Type 1R dilated cardiomyopathy and Type 11 hypertrophic cardiomyopathy. Certain defects of the atrial septum have been described recently that could also be related to these mutations.[113][114]

    Two cases of dilated cardiomyopathy have been studied involving a substitution of highly conserved amino acids belonging to the protein domains that bind and intersperse with the Z discs. This has led to the theory that the dilation is produced by a defect in the transmission of contractile force in the myocytes.[28][111]

    The mutations in”ACTC1” are responsible for at least 5% of hypertrophic cardiomyopathies.[115] The existence of a number of point mutations have also been found:[116]

    • Mutation E101K: changes of net charge and formation of a weak electrostatic link in the actomyosin-binding site.
    • P166A: interaction zone between actin monomers.
    • A333P: actin-myosin interaction zone.

    Pathogenesis appears to involve a compensatory mechanism: the mutated proteins act like “toxins” with a dominant effect, decreasing the heart’s ability to contract causing abnormal mechanical behaviour such that the hypertrophy, that is usually delayed, is a consequence of the cardiac muscle’s normal response to stress.[117]

    Recent studies have discovered “ACTC1” mutations that are implicated in two other pathological processes: Infantile idiopathic restrictive cardiomyopathy,[118] and noncompaction of the left ventricular myocardium.[119]

    In cytoplasmatic actins

    ACTB is a highly complex locus. A number of pseudogenes exist that are distributed throughout the genome, and its sequence contains six exons that can give rise to up to 21 different transcriptions by alternative splicing, which are known as the β-actins. Consistent with this complexity, its products are also found in a number of locations and they form part of a wide variety of processes (cytoskeleton, NuA4 histone-acyltransferase complex, cell nucleus) and in addition they are associated with the mechanisms of a great number of pathological processes (carcinomas, juvenile dystonia, infection mechanisms, nervous system malformations and tumour invasion, among others).[120] A new form of actin has been discovered, kappa actin, which appears to substitute for β-actin in processes relating to tumours.[121]

    Image taken using confocal microscopy and employing the use of specific antibodies showing actin’s cortical network. In the same way that in juvenile dystonia there is an interruption in the structures of the cytoskeleton, in this case it is produced by cytochalasin D.[122]

    Three pathological processes have so far been discovered that are caused by a direct alteration in gene sequence:

    The ACTG1 locus codes for the cytosolic γ-actin protein that is responsible for the formation of cytoskeletal microfilaments. It contains six exons, giving rise to 22 different mRNAs, which produce four complete isoforms whose form of expression is probably dependent on the type of tissue they are found in. It also has two different DNA promoters.[126] It has been noted that the sequences translated from this locus and from that of β-actin are very similar to the predicted ones, suggesting a common ancestral sequence that suffered duplication and genetic conversion.[127]

    In terms of pathology, it has been associated with processes such as amyloidosis, retinitis pigmentosa, infection mechanisms, kidney diseases and various types of congenital hearing loss.[126]

    Six autosomal-dominant point mutations in the sequence have been found to cause various types of hearing loss, particularly sensorineural hearing loss linked to the DFNA 20/26 locus. It seems that they affect the

    External links

    1. ^ a b c d e ​; Otterbein LR, Graceffa P, Dominguez R (Jul 2001). "The crystal structure of uncomplexed actin in the ADP state". Science 293 (5530): 708–11.  
    2. ^ Doherty GJ, McMahon HT (2008). "Mediation, modulation, and consequences of membrane-cytoskeleton interactions". Annual Review of Biophysics 37 (1): 65–95.  
    3. ^ Vindin H, Gunning P (Aug 2013). "Cytoskeletal tropomyosins: choreographers of actin filament functional diversity". Journal of Muscle Research and Cell Motility 34 (3-4): 261–74.  
    4. ^ a b c d e f g h i Gunning PW, Ghoshdastider U, Whitaker S, Popp D, Robinson RC (Jun 2015). "The evolution of compositionally and functionally distinct actin filaments". Journal of Cell Science 128 (11): 2009–19.  
    5. ^ Ghoshdastider U, Jiang S, Popp D, Robinson RC. "In search of the primordial actin filament.". Proc Natl Acad Sci U S A. 112 (30): 9150–1.  
    6. ^ a b Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002). "Chapter 16: The cytoskeleton". Molecular biology of the cell. New York: Garland Science. pp. 907–982.  
    7. ^ Halliburton WD (Aug 1887). "On Muscle-Plasma". The Journal of Physiology 8 (3-4): 133–202.  
    8. ^ Szent-Gyorgyi A (1945). "Studies on muscle". Acta Physiol Scandinav 9 (Suppl): 25. 
    9. ^ a b Straub FB, Feuer G (1989). "Adenosinetriphosphate. The functional group of actin. 1950". Biochimica Et Biophysica Acta 1000: 180–95.  
    10. ^ Bárány M, Barron JT, Gu L, Bárány K (Dec 2001). "Exchange of the actin-bound nucleotide in intact arterial smooth muscle". The Journal of Biological Chemistry 276 (51): 48398–403.  
    11. ^ a b c Elzinga M, Collins JH, Kuehl WM, Adelstein RS (Sep 1973). "Complete amino-acid sequence of actin of rabbit skeletal muscle". Proceedings of the National Academy of Sciences of the United States of America 70 (9): 2687–91.  
    12. ^ a b Kabsch W, Mannherz HG, Suck D, Pai EF, Holmes KC (Sep 1990). "Atomic structure of the actin:DNase I complex". Nature 347 (6288): 37–44.  
    13. ^ a b Holmes KC, Popp D, Gebhard W, Kabsch W (September 1990). "Atomic model of the actin filament". Nature 347 (6288): 44–9.  
    14. ^ Oriol C, Dubord C, Landon F (Jan 1977). "Crystallization of native striated-muscle actin". FEBS Letters 73 (1): 89–91.  
    15. ^ Sawaya MR, Kudryashov DS, Pashkov I, Adisetiyo H, Reisler E, Yeates TO (Apr 2008). "Multiple crystal structures of actin dimers and their implications for interactions in the actin filament". Acta Crystallographica. Section D, Biological Crystallography 64 (Pt 4): 454–65.  
    16. ^ Narita A, Takeda S, Yamashita A, Maéda Y (Nov 2006). "Structural basis of actin filament capping at the barbed-end: a cryo-electron microscopy study". The EMBO Journal 25 (23): 5626–33.  
    17. ^ a b c d e f Oda T, Iwasa M, Aihara T, Maéda Y, Narita A (Jan 2009). "The nature of the globular- to fibrous-actin transition". Nature 457 (7228): 441–5.  
    18. ^ a b c d Biología celular (in Spanish). Elsevier España. 2002. p. 132.  
    19. ^ Ponte P, Gunning P, Blau H, Kedes L (Oct 1983). "Human actin genes are single copy for alpha-skeletal and alpha-cardiac actin but multicopy for beta- and gamma-cytoskeletal genes: 3' untranslated regions are isotype specific but are conserved in evolution". Molecular and Cellular Biology 3 (10): 1783–91.  
    20. ^ a b c d Scott MP, Lodish HF, Berk A, Kaiser C, Krieger M, Bretscher A, Ploegh H, Amon A (2012). Molecular Cell Biology. San Francisco: W. H. Freeman.  
    21. ^ Hara F, Yamashiro K, Nemoto N, Ohta Y, Yokobori S, Yasunaga T, Hisanaga S, Yamagishi A (Mar 2007). "An actin homolog of the archaeon Thermoplasma acidophilum that retains the ancient characteristics of eukaryotic actin". Journal of Bacteriology 189 (5): 2039–45.  
    22. ^ a b Graceffa P, Dominguez R (Sep 2003). "Crystal structure of monomeric actin in the ATP state. Structural basis of nucleotide-dependent actin dynamics". The Journal of Biological Chemistry 278 (36): 34172–80.  
    23. ^ Reisler E (Feb 1993). "Actin molecular structure and function". Current Opinion in Cell Biology 5 (1): 41–7.  
    24. ^ "cd00012: ACTIN". Conserved Domain Database. U.S. National Center for Biotechnology Information (NCBI). 
    25. ^ a b Collins JH, Elzinga M (Aug 1975). "The primary structure of actin from rabbit skeletal muscle. Completion and analysis of the amino acid sequence". The Journal of Biological Chemistry 250 (15): 5915–20.  
    26. ^ a b c d e f g h Dos Remedios CG, Chhabra D (2008). Actin-binding Proteins and Disease. Springer.  
    27. ^ Rould MA, Wan Q, Joel PB, Lowey S, Trybus KM (Oct 2006). "Crystal structures of expressed non-polymerizable monomeric actin in the ADP and ATP states". The Journal of Biological Chemistry 281 (42): 31909–19.  
    28. ^ a b Devlin TM (2006). Bioquimica. Barcelona: Reverté.  
    29. ^ a b c Reisler E, Egelman EH (Dec 2007). "Actin structure and function: what we still do not understand". The Journal of Biological Chemistry 282 (50): 36133–7.  
    30. ^ Begg DA, Rodewald R, Rebhun LI (Dec 1978). "The visualization of actin filament polarity in thin sections. Evidence for the uniform polarity of membrane-associated filaments". The Journal of Cell Biology 79 (3): 846–52.  
    31. ^ Geneser F (1981). Histologi. Munksgaard. p. 105.  
    32. ^ a b c Hall JE, Guyton AC (2006). Textbook of medical physiology. St. Louis, Mo: Elsevier Saunders. p. 76.  
    33. ^ a b Simons CT, Staes A, Rommelaere H, Ampe C, Lewis SA, Cowan NJ (Feb 2004). "Selective contribution of eukaryotic prefoldin subunits to actin and tubulin binding". The Journal of Biological Chemistry 279 (6): 4196–203.  
    34. ^ a b Martín-Benito J, Boskovic J, Gómez-Puertas P, Carrascosa JL, Simons CT, Lewis SA, Bartolini F, Cowan NJ, Valpuesta JM (Dec 2002). "Structure of eukaryotic prefoldin and of its complexes with unfolded actin and the cytosolic chaperonin CCT". The EMBO Journal 21 (23): 6377–86.  
    35. ^ a b Vandamme D, Lambert E, Waterschoot D, Cognard C, Vandekerckhove J, Ampe C, Constantin B, Rommelaere H (Jul 2009). "alpha-Skeletal muscle actin nemaline myopathy mutants cause cell death in cultured muscle cells". Biochimica Et Biophysica Acta 1793 (7): 1259–71.  
    36. ^ a b Brackley KI, Grantham J (Jan 2009). "Activities of the chaperonin containing TCP-1 (CCT): implications for cell cycle progression and cytoskeletal organisation". Cell Stress & Chaperones 14 (1): 23–31.  
    37. ^ a b Stirling PC, Cuéllar J, Alfaro GA, El Khadali F, Beh CT, Valpuesta JM, Melki R, Leroux MR (Mar 2006). "PhLP3 modulates CCT-mediated actin and tubulin folding via ternary complexes with substrates". The Journal of Biological Chemistry 281 (11): 7012–21.  
    38. ^ Hansen WJ, Cowan NJ, Welch WJ (Apr 1999). "Prefoldin-nascent chain complexes in the folding of cytoskeletal proteins". The Journal of Cell Biology 145 (2): 265–77.  
    39. ^ Martín-Benito J, Grantham J, Boskovic J, Brackley KI, Carrascosa JL, Willison KR, Valpuesta JM (Mar 2007). "The inter-ring arrangement of the cytosolic chaperonin CCT". EMBO Reports 8 (3): 252–7.  
    40. ^ Neirynck K, Waterschoot D, Vandekerckhove J, Ampe C, Rommelaere H (Jan 2006). "Actin interacts with CCT via discrete binding sites: a binding transition-release model for CCT-mediated actin folding". Journal of Molecular Biology 355 (1): 124–38.  
    41. ^ a b c Vavylonis D, Yang Q, O'Shaughnessy B (Jun 2005). "Actin polymerization kinetics, cap structure, and fluctuations". Proceedings of the National Academy of Sciences of the United States of America 102 (24): 8543–8.  
    42. ^ Vandekerckhove J, Weber K (Dec 1978). "At least six different actins are expressed in a higher mammal: an analysis based on the amino acid sequence of the amino-terminal tryptic peptide". Journal of Molecular Biology 126 (4): 783–802.  
    43. ^ Khaitlina SY (2001). "Functional specificity of actin isoforms". International Review of Cytology 202: 35–98.  
    44. ^ Garner EC, Campbell CS, Weibel DB, Mullins RD (Mar 2007). "Reconstitution of DNA segregation driven by assembly of a prokaryotic actin homolog". Science 315 (5816): 1270–4.  
    45. ^ Kawamura M, Maruyama K (Mar 1970). "Electron microscopic particle length of F-actin polymerized in vitro". Journal of Biochemistry 67 (3): 437–57.  
    46. ^ Hausman RE, Cooper GM (2007). "Chapter 12: The Cytoskeleton and Cell Movement". The cell: a molecular approach. Washington, DC :, Sunderland, MA: ASM Press, Sinauer Associates.  
    47. ^ Bindschadler M, Osborn EA, Dewey CF, McGrath JL (May 2004). "A mechanistic model of the actin cycle". Biophysical Journal 86 (5): 2720–39.  
    48. ^ Kirschner MW (Jul 1980). "Implications of treadmilling for the stability and polarity of actin and tubulin polymers in vivo". The Journal of Cell Biology 86 (1): 330–4.  
    49. ^ Ghodsi H, Kazemi MT (June 2011). "Elastic Properties of Actin Assemblies in Different States of Nucleotide Binding". Cell. Mol. Bioeng. 5 (1): 1–13.  
    50. ^ Plopper G, Lewin B, Cassimeris L (2007). Cells. Boston: Jones and Bartlett Publishers.  
    51. ^ Zhang DS, Piazza V, Perrin BJ, Rzadzinska AK, Poczatek JC, Wang M, Prosser HM, Ervasti JM, Corey DP, Lechene CP (Jan 2012). "Multi-isotope imaging mass spectrometry reveals slow protein turnover in hair-cell stereocilia". Nature 481 (7382): 520–4.  
    52. ^ ​; Schutt CE, Myslik JC, Rozycki MD, Goonesekere NC, Lindberg U (October 1993). "The structure of crystalline profilin-beta-actin". Nature 365 (6449): 810–6.  
    53. ^ Dominguez R (Nov 2004). "Actin-binding proteins--a unifying hypothesis". Trends in Biochemical Sciences 29 (11): 572–8.  
    54. ^ Goldschmidt-Clermont PJ, Furman MI, Wachsstock D, Safer D, Nachmias VT, Pollard TD (Sep 1992). "The control of actin nucleotide exchange by thymosin beta 4 and profilin. A potential regulatory mechanism for actin polymerization in cells". Molecular Biology of the Cell 3 (9): 1015–24.  
    55. ^ Witke W, Podtelejnikov AV, Di Nardo A, Sutherland JD, Gurniak CB, Dotti C, Mann M (Feb 1998). "In mouse brain profilin I and profilin II associate with regulators of the endocytic pathway and actin assembly". The EMBO Journal 17 (4): 967–76.  
    56. ^ Carlsson L, Nyström LE, Sundkvist I, Markey F, Lindberg U (Sep 1977). "Actin polymerizability is influenced by profilin, a low molecular weight protein in non-muscle cells". Journal of Molecular Biology 115 (3): 465–83.  
    57. ^ Kiselar JG, Janmey PA, Almo SC, Chance MR (April 2003). "Visualizing the Ca2+-dependent activation of gelsolin by using synchrotron footprinting". Proc. Natl. Acad. Sci. U.S.A. 100 (7): 3942–7.  
    58. ^ Ghoshdastider U, Popp D, Burtnick LD, Robinson RC (2013). "The expanding superfamily of gelsolin homology domain proteins". Cytoskeleton (Hoboken) 70 (11): 775–95.  
    59. ^ Southwick FS (Jun 2000). "Gelsolin and ADF/cofilin enhance the actin dynamics of motile cells". Proceedings of the National Academy of Sciences of the United States of America 97 (13): 6936–8.  
    60. ^ Caldwell JE, Heiss SG, Mermall V, Cooper JA (Oct 1989). "Effects of CapZ, an actin capping protein of muscle, on the polymerization of actin". Biochemistry 28 (21): 8506–14.  
    61. ^ Weber A, Pennise CR, Babcock GG, Fowler VM (Dec 1994). "Tropomodulin caps the pointed ends of actin filaments". The Journal of Cell Biology 127 (6 Pt 1): 1627–35.  
    62. ^ Robinson RC, Turbedsky K, Kaiser DA, Marchand JB, Higgs HN, Choe S, Pollard TD (November 2001). "Crystal structure of Arp2/3 complex". Science 294 (5547): 1679–84.  
    63. ^ Mullins RD, Pollard TD (Apr 1999). "Structure and function of the Arp2/3 complex". Current Opinion in Structural Biology 9 (2): 244–9.  
    64. ^ Machesky LM, Gould KL (Feb 1999). "The Arp2/3 complex: a multifunctional actin organizer". Current Opinion in Cell Biology 11 (1): 117–21.  
    65. ^ Morton WM, Ayscough KR, McLaughlin PJ (Jun 2000). "Latrunculin alters the actin-monomer subunit interface to prevent polymerization". Nature Cell Biology 2 (6): 376–8.  
    66. ^ a b Cooper JA (Oct 1987). "Effects of cytochalasin and phalloidin on actin". The Journal of Cell Biology 105 (4): 1473–8.  
    67. ^ Rubtsova SN, Kondratov RV, Kopnin PB, Chumakov PM, Kopnin BP, Vasiliev JM (Jul 1998). "Disruption of actin microfilaments by cytochalasin D leads to activation of p53". FEBS Letters 430 (3): 353–7.  
    68. ^ Huber F, Schnauß J, Rönicke S, Rauch P, Müller K, Fütterer C, Käs J (Jan 2013). "Emergent complexity of the cytoskeleton: from single filaments to tissue". Advances in Physics 62 (1): 1–112.   online
    69. ^ a b Grummt I (Apr 2006). "Actin and myosin as transcription factors". Current Opinion in Genetics & Development 16 (2): 191–6.  
    70. ^ Zouwail S, Pettitt TR, Dove SK, Chibalina MV, Powner DJ, Haynes L, Wakelam MJ, Insall RH (Jul 2005). "Phospholipase D activity is essential for actin localization and actin-based motility in Dictyostelium". The Biochemical Journal 389 (Pt 1): 207–14.  
    71. ^ a b Eckert R, Randall D, Burggren WW, French K (2002). Eckert animal physiology: mechanisms and adaptations. New York: W.H. Freeman and CO.  
    72. ^ Trombocitopenias (Spanish Edition) (2nd ed.). Elsevier Espana. 2001. p. 25.  
    73. ^ a b c Paniagua R, Nistal M, Sesma P, Álvarez-Uría M, Fraile B, Anadón R, José Sáez F (2002). Citología e histología vegetal y animal (in Spanish). McGraw-Hill Interamericana de España, S.A.U.  
    74. ^ Xu K, Zhong G, Zhuang X (Jan 2013). "Actin, spectrin, and associated proteins form a periodic cytoskeletal structure in axons". Science 339 (6118): 452–6.  
    75. ^ a b Moseley JB, Goode BL (Sep 2006). "The yeast actin cytoskeleton: from cellular function to biochemical mechanism". Microbiology and Molecular Biology Reviews 70 (3): 605–45.  
    76. ^ Meagher RB, McKinney EC, Kandasamy MK (Jun 1999). "Isovariant dynamics expand and buffer the responses of complex systems: the diverse plant actin gene family". The Plant Cell 11 (6): 995–1006.  
    77. ^  
    78. ^ a b Higaki T, Sano T, Hasezawa S (Dec 2007). "Actin microfilament dynamics and actin side-binding proteins in plants". Current Opinion in Plant Biology 10 (6): 549–56.  
    79. ^ Kovar DR, Staiger CJ, Weaver EA, McCurdy DW (Dec 2000). "AtFim1 is an actin filament crosslinking protein from Arabidopsis thaliana". The Plant Journal 24 (5): 625–36.  
    80. ^ Zheng B, Han M, Bernier M, Wen JK (May 2009). "Nuclear actin and actin-binding proteins in the regulation of transcription and gene expression". The FEBS Journal 276 (10): 2669–85.  
    81. ^ de Luna AB, Staff VV, López-Sendón J, Attie F, Ezquerra EA (2003). Cardiología clínica. Elsevier España.  
    82. ^ a b Dominiczak MH, Baynes J (2005). Bioquimica Medica: con acceso a Student Consult (Spanish Edition). Elsevier Espana.  
    83. ^ Fujiwara K, Porter ME, Pollard TD (Oct 1978). "Alpha-actinin localization in the cleavage furrow during cytokinesis". The Journal of Cell Biology 79 (1): 268–75.  
    84. ^ Pelham RJ, Chang F (Sep 2002). "Actin dynamics in the contractile ring during cytokinesis in fission yeast". Nature 419 (6902): 82–6.  
    85. ^ Mashima T, Naito M, Noguchi K, Miller DK, Nicholson DW, Tsuruo T (Mar 1997). "Actin cleavage by CPP-32/apopain during the development of apoptosis". Oncogene 14 (9): 1007–12.  
    86. ^ Wang KK (Jan 2000). "Calpain and caspase: can you tell the difference?". Trends in Neurosciences 23 (1): 20–6.  
    87. ^ Villa PG, Henzel WJ, Sensenbrenner M, Henderson CE, Pettmann B (Mar 1998). "Calpain inhibitors, but not caspase inhibitors, prevent actin proteolysis and DNA fragmentation during apoptosis". Journal of Cell Science. 111 ( Pt 6) (Pt 6): 713–22.  
    88. ^ Huot J, Houle F, Rousseau S, Deschesnes RG, Shah GM, Landry J (Nov 1998). "SAPK2/p38-dependent F-actin reorganization regulates early membrane blebbing during stress-induced apoptosis". The Journal of Cell Biology 143 (5): 1361–73.  
    89. ^ Adams CL, Nelson WJ, Smith SJ (Dec 1996). "Quantitative analysis of cadherin-catenin-actin reorganization during development of cell-cell adhesion". The Journal of Cell Biology 135 (6 Pt 2): 1899–911.  
    90. ^ Witke W, Schleicher M, Noegel AA (Jan 1992). "Redundancy in the microfilament system: abnormal development of Dictyostelium cells lacking two F-actin cross-linking proteins". Cell 68 (1): 53–62.  
    91. ^ Fernandez-Valle C, Gorman D, Gomez AM, Bunge MB (Jan 1997). "Actin plays a role in both changes in cell shape and gene-expression associated with Schwann cell myelination". The Journal of Neuroscience 17 (1): 241–50.  
    92. ^ Wolyniak MJ, Sundstrom P (Oct 2007). "Role of actin cytoskeletal dynamics in activation of the cyclic AMP pathway and HWP1 gene expression in Candida albicans". Eukaryotic Cell 6 (10): 1824–40.  
    93. ^ Tanaka H, Iguchi N, Egydio de Carvalho C, Tadokoro Y, Yomogida K, Nishimune Y (Aug 2003). "Novel actin-like proteins T-ACTIN 1 and T-ACTIN 2 are differentially expressed in the cytoplasm and nucleus of mouse haploid germ cells". Biology of Reproduction 69 (2): 475–82.  
    94. ^ Jiang YW, Stillman DJ (Mar 1996). "Epigenetic effects on yeast transcription caused by mutations in an actin-related protein present in the nucleus". Genes & Development 10 (5): 604–19.  
    95. ^ Manor U, Kachar B (Dec 2008). "Dynamic length regulation of sensory stereocilia". Seminars in Cell & Developmental Biology 19 (6): 502–10.  
    96. ^ Rzadzinska AK, Schneider ME, Davies C, Riordan GP, Kachar B (Mar 2004). "An actin molecular treadmill and myosins maintain stereocilia functional architecture and self-renewal". The Journal of Cell Biology 164 (6): 887–97.  
    97. ^ Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, Zhang J, Soden R, Hayakawa M, Kreiman G, Cooke MP, Walker JR, Hogenesch JB (Apr 2004). "A gene atlas of the mouse and human protein-encoding transcriptomes". Proceedings of the National Academy of Sciences of the United States of America 101 (16): 6062–7.  
    98. ^ a b "ACTS_HUMAN". P68133. UniProt Consortium. Retrieved 2013-01-21. 
    99. ^ a b Bathe FS, Rommelaere H, Machesky LM (2007). "Phenotypes of myopathy-related actin mutants in differentiated C2C12 myotubes". BMC Cell Biol. 8 (1): 2.  
    100. ^ Kaindl AM, Rüschendorf F, Krause S, Goebel HH, Koehler K, Becker C, Pongratz D, Müller-Höcker J, Nürnberg P, Stoltenburg-Didinger G, Lochmüller H, Huebner A (Nov 2004). "Missense mutations of ACTA1 cause dominant congenital myopathy with cores". Journal of Medical Genetics 41 (11): 842–8.  
    101. ^ Sparrow JC, Nowak KJ, Durling HJ, Beggs AH, Wallgren-Pettersson C, Romero N, Nonaka I, Laing NG (Sep 2003). "Muscle disease caused by mutations in the skeletal muscle alpha-actin gene (ACTA1)". Neuromuscular Disorders 13 (7-8): 519–31.  
    102. ^ North K, Ryan MM (2002). "Nemaline Myopathy". In Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle. 
    103. ^ Ilkovski B, Nowak KJ, Domazetovska A, Maxwell AL, Clement S, Davies KE, Laing NG, North KN, Cooper ST (Aug 2004). "Evidence for a dominant-negative effect in ACTA1 nemaline myopathy caused by abnormal folding, aggregation and altered polymerization of mutant actin isoforms". Human Molecular Genetics 13 (16): 1727–43.  
    104. ^ Clarke NF, Ilkovski B, Cooper S, Valova VA, Robinson PJ, Nonaka I, Feng JJ, Marston S, North K (Jun 2007). "The pathogenesis of ACTA1-related congenital fiber type disproportion". Annals of Neurology 61 (6): 552–61.  
    105. ^ a b Miwa T, Manabe Y, Kurokawa K, Kamada S, Kanda N, Bruns G, Ueyama H, Kakunaga T (Jun 1991). "Structure, chromosome location, and expression of the human smooth muscle (enteric type) gamma-actin gene: evolution of six human actin genes". Molecular and Cellular Biology 11 (6): 3296–306.  
    106. ^ Watson MB, Lind MJ, Smith L, Drew PJ, Cawkwell L (2007). "Expression microarray analysis reveals genes associated with in vitro resistance to cisplatin in a cell line model". Acta Oncologica 46 (5): 651–8.  
    107. ^ Guo DC, Pannu H, Tran-Fadulu V, Papke CL, Yu RK, Avidan N, Bourgeois S, Estrera AL, Safi HJ, Sparks E, Amor D, Ades L, McConnell V, Willoughby CE, Abuelo D, Willing M, Lewis RA, Kim DH, Scherer S, Tung PP, Ahn C, Buja LM, Raman CS, Shete SS, Milewicz DM (Dec 2007). "Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections". Nature Genetics 39 (12): 1488–93.  
    108. ^ Guo DC, Papke CL, Tran-Fadulu V, Regalado ES, Avidan N, Johnson RJ, Kim DH, Pannu H, Willing MC, Sparks E, Pyeritz RE, Singh MN, Dalman RL, Grotta JC, Marian AJ, Boerwinkle EA, Frazier LQ, LeMaire SA, Coselli JS, Estrera AL, Safi HJ, Veeraraghavan S, Muzny DM, Wheeler DA, Willerson JT, Yu RK, Shete SS, Scherer SE, Raman CS, Buja LM, Milewicz DM (May 2009). "Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease". American Journal of Human Genetics 84 (5): 617–27.  
    109. ^ Akpolat N, Yahsi S, Godekmerdan A, Yalniz M, Demirbag K (Sep 2005). "The value of alpha-SMA in the evaluation of hepatic fibrosis severity in hepatitis B infection and cirrhosis development: a histopathological and immunohistochemical study". Histopathology 47 (3): 276–80.  
    110. ^ Hamada H, Petrino MG, Kakunaga T (Oct 1982). "Molecular structure and evolutionary origin of human cardiac muscle actin gene". Proceedings of the National Academy of Sciences of the United States of America 79 (19): 5901–5.  
    111. ^ a b Olson TM, Michels VV, Thibodeau SN, Tai YS, Keating MT (May 1998). "Actin mutations in dilated cardiomyopathy, a heritable form of heart failure". Science 280 (5364): 750–2.  
    112. ^ Xia XG, Zhou H, Samper E, Melov S, Xu Z (January 2006). "Pol II-expressed shRNA knocks down Sod2 gene expression and causes phenotypes of the gene knockout in mice". PLoS Genet. 2 (1): e10.  
    113. ^ Online 'Mendelian Inheritance in Man' (OMIM) Actin, alpha, cardiac muscle; ACTC1 -102540
    114. ^ Matsson H, Eason J, Bookwalter CS, Klar J, Gustavsson P, Sunnegårdh J, Enell H, Jonzon A, Vikkula M, Gutierrez I, Granados-Riveron J, Pope M, Bu'Lock F, Cox J, Robinson TE, Song F, Brook DJ, Marston S, Trybus KM, Dahl N (Jan 2008). "Alpha-cardiac actin mutations produce atrial septal defects". Human Molecular Genetics 17 (2): 256–65.  
    115. ^ Kabaeva Z (2002). Genetic analysis in hypertrophic cardiomyopathy: missense mutations in the ventricular myosin regulatory light chain gene (Doctor medicinae). Humboldt-Universität zu Berlin. Retrieved 2013-01-21. 
    116. ^ Olson TM, Doan TP, Kishimoto NY, Whitby FG, Ackerman MJ, Fananapazir L (Sep 2000). "Inherited and de novo mutations in the cardiac actin gene cause hypertrophic cardiomyopathy". Journal of Molecular and Cellular Cardiology 32 (9): 1687–94.  
    117. ^ Ramírez CD, Ramírez RP (March 2004). "Cardiomiopatía hipertrófica familiar: Genes, mutaciones y modelos animales. Revisión". Invest. Clín (in Spanish) 45 (1): 69–100. 
    118. ^ Kaski JP, Syrris P, Burch M, Tomé-Esteban MT, Fenton M, Christiansen M, Andersen PS, Sebire N, Ashworth M, Deanfield JE, McKenna WJ, Elliott PM (Nov 2008). "Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes". Heart 94 (11): 1478–84.  
    119. ^ Pigott TJ, Jefferson D (1991). "Idiopathic common peroneal nerve palsy--a review of thirteen cases". British Journal of Neurosurgery 5 (1): 7–11.  
    120. ^ "Gene: ACTB". AceView. U.S. National Center for Biotechnology Information (NCBI). Retrieved 2013-01-21. 
    121. ^ Chang KW, Yang PY, Lai HY, Yeh TS, Chen TC, Yeh CT (Sep 2006). "Identification of a novel actin isoform in hepatocellular carcinoma". Hepatology Research 36 (1): 33–9.  
    122. ^ Williams KL, Rahimtula M, Mearow KM (2005). "Hsp27 and axonal growth in adult sensory neurons in vitro". BMC Neurosci 6 (1): 24.  
    123. ^ "Soft tissue tumors: Pericytoma with t(7;12)". Atlas of Genetics and Cytogenetics in Oncology and Haematology. University Hospital of Poitiers. Retrieved 2013-01-21. 
    124. ^ Procaccio V, Salazar G, Ono S, Styers ML, Gearing M, Davila A, Jimenez R, Juncos J, Gutekunst CA, Meroni G, Fontanella B, Sontag E, Sontag JM, Faundez V, Wainer BH (Jun 2006). "A mutation of beta -actin that alters depolymerization dynamics is associated with autosomal dominant developmental malformations, deafness, and dystonia". American Journal of Human Genetics 78 (6): 947–60.  
    125. ^ Nunoi H, Yamazaki T, Tsuchiya H, Kato S, Malech HL, Matsuda I, Kanegasaki S (Jul 1999). "A heterozygous mutation of beta-actin associated with neutrophil dysfunction and recurrent infection". Proceedings of the National Academy of Sciences of the United States of America 96 (15): 8693–8.  
    126. ^ a b "Gene: ACTG1". AceView. U.S. National Center for Biotechnology Information (NCBI). Retrieved 2013-01-21. 
    127. ^ Erba HP, Gunning P, Kedes L (Jul 1986). "Nucleotide sequence of the human gamma cytoskeletal actin mRNA: anomalous evolution of vertebrate non-muscle actin genes". Nucleic Acids Research 14 (13): 5275–94.  
    128. ^ Bryan KE, Rubenstein PA (Jul 2009). "Allele-specific effects of human deafness gamma-actin mutations (DFNA20/26) on the actin/cofilin interaction". The Journal of Biological Chemistry 284 (27): 18260–9.  
    129. ^ Sonnemann KJ, Fitzsimons DP, Patel JR, Liu Y, Schneider MF, Moss RL, Ervasti JM (Sep 2006). "Cytoplasmic gamma-actin is not required for skeletal muscle development but its absence leads to a progressive myopathy". Developmental Cell 11 (3): 387–97.  
    130. ^ Gouin E, Gantelet H, Egile C, Lasa I, Ohayon H, Villiers V, Gounon P, Sansonetti PJ, Cossart P (Jun 1999). "A comparative study of the actin-based motilities of the pathogenic bacteria Listeria monocytogenes, Shigella flexneri and Rickettsia conorii" (PDF). Journal of Cell Science. 112 ( Pt 11) (Pt 11): 1697–708.  
    131. ^ Lambrechts A, Gevaert K, Cossart P, Vandekerckhove J, Van Troys M (May 2008). "Listeria comet tails: the actin-based motility machinery at work". Trends in Cell Biology 18 (5): 220–7.  
    132. ^ Gouin E, Welch MD, Cossart P (Feb 2005). "Actin-based motility of intracellular pathogens". Current Opinion in Microbiology 8 (1): 35–45.  
    133. ^ Parks QM, Young RL, Poch KR, Malcolm KC, Vasil ML, Nick JA (Apr 2009). "Neutrophil enhancement of Pseudomonas aeruginosa biofilm development: human F-actin and DNA as targets for therapy". Journal of Medical Microbiology 58 (Pt 4): 492–502.  
    134. ^ Liu Y, Belkina NV, Shaw S (2009). "HIV infection of T cells: actin-in and actin-out". Science Signaling 2 (66): pe23.  
    135. ^ Machesky LM, Tang HR (Jul 2009). "Actin-based protrusions: promoters or inhibitors of cancer invasion?". Cancer Cell 16 (1): 5–7.  
    136. ^ Erickson HP (Jul 2007). "Evolution of the cytoskeleton". BioEssays 29 (7): 668–77.  
    137. ^ Gardiner J, McGee P, Overall R, Marc J (2008). "Are histones, tubulin, and actin derived from a common ancestral protein?". Protoplasma 233 (1-2): 1–5.  
    138. ^ Galletta BJ, Cooper JA (Feb 2009). "Actin and endocytosis: mechanisms and phylogeny". Current Opinion in Cell Biology 21 (1): 20–7.  
    139. ^ Popp D, Narita A, Maeda K, Fujisawa T, Ghoshdastider U, Iwasa M, Maéda Y, Robinson RC (May 2010). "Filament structure, organization, and dynamics in MreB sheets". The Journal of Biological Chemistry 285 (21): 15858–65.  
    140. ^ van den Ent F, Amos LA, Löwe J (Sep 2001). "Prokaryotic origin of the actin cytoskeleton". Nature 413 (6851): 39–44.  
    141. ^ Carballido-López R (Dec 2006). "The bacterial actin-like cytoskeleton". Microbiology and Molecular Biology Reviews 70 (4): 888–909.  
    142. ^ Popp D, Xu W, Narita A, Brzoska AJ, Skurray RA, Firth N, Ghoshdastider U, Goshdastider U, Maéda Y, Robinson RC, Schumacher MA (Mar 2010). "Structure and filament dynamics of the pSK41 actin-like ParM protein: implications for plasmid DNA segregation". The Journal of Biological Chemistry 285 (13): 10130–40.  
    143. ^ Popp D, Narita A, Ghoshdastider U, Maeda K, Maéda Y, Oda T, Fujisawa T, Onishi H, Ito K, Robinson RC (Apr 2010). "Polymeric structures and dynamic properties of the bacterial actin AlfA". Journal of Molecular Biology 397 (4): 1031–41.  
    144. ^ Popp D, Narita A, Lee LJ, Ghoshdastider U, Xue B, Srinivasan R, Balasubramanian MK, Tanaka T, Robinson RC (Jun 2012). "Novel actin-like filament structure from Clostridium tetani". The Journal of Biological Chemistry 287 (25): 21121–9.  
    145. ^ Hess H, Clemmens J, Qin D, Howard J, Vogel V (2001). "Light-controlled molecular shuttles made from motor proteins carrying cargo on engineered surfaces". Nano Letters 1 (5): 235–239.  
    146. ^ Mansson A, Sundberg M, Bunk R, Balaz M, Nicholls IA, Omling P, Tegenfeldt JO, Tagerud S, Montelius L (2005). "Actin-Based Molecular Motors for Cargo Transportation in Nanotechnology—Potentials and Challenges". IEEE Transactions on Advanced Packaging 28 (4): 547–555.  
    147. ^ Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (Jun 2002). "Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes". Genome Biology 3 (7): RESEARCH0034.  
    148. ^ Selvey S, Thompson EW, Matthaei K, Lea RA, Irving MG, Griffiths LR (Oct 2001). "Beta-actin--an unsuitable internal control for RT-PCR". Molecular and Cellular Probes 15 (5): 307–11.  
    149. ^ Mukai K, Schollmeyer JV, Rosai J (Jan 1981). "Immunohistochemical localization of actin: applications in surgical pathology". The American Journal of Surgical Pathology 5 (1): 91–7.  
    150. ^ Haddad F, Roy RR, Zhong H, Edgerton VR, Baldwin KM (Aug 2003). "Atrophy responses to muscle inactivity. II. Molecular markers of protein deficits". Journal of Applied Physiology 95 (2): 791–802.  
    151. ^ Hocquette JF, Lehnert S, Barendse W, Cassar-Malek I, Picard B (2006). "Current advances in proteomic analysis and its use for the resolution of poultry meat quality" (PDF). World's Poultry Science Journal 62 (1): 123–130.  
    152. ^ Nollet L (2004). "Methods and Instruments in Applied Food Analysis". Handbook of food analysis 3 (2 ed.). New York, N.Y: Marcel Dekker. pp. 1741–2226.  


    See also

    • nanotechnology as its dynamic ability has been harnessed in a number of experiments including those carried out in acellular systems. The underlying idea is to use the microfilaments as tracks to guide molecular motors that can transport a given load. That is actin could be used to define a circuit along which a load can be transported in a more or less controlled and directed manner. In terms of general applications, it could be used for the directed transport of molecules for deposit in determined locations, which would permit the controlled assembly of nanostructures.[145] These attributes could be applied to laboratory processes such as on lab-on-a-chip, in nanocomponent mechanics and in nanotransformers that convert mechanical energy into electrical energy.[146]
    • Internal control of techniques used in molecular biology, such as western blot and quantitative PCR. As actin is essential for cell survival it has been postulated that the quantity of actin is under such tight control at a cellular level that it can be assumed that its transcription (that is, the degree to which its genes are expressed) and translation, that is the production of protein, is practically constant and independent of experimental conditions. Therefore, it is common practice in protein quantification studies (western blot) and transcription studies (quantitative PCR) to carry out the quantification of the gene of interest and also the quantification of a reference gene such as the one that codes for actin. By dividing the quantity of the gene of interest by that of the actin gene it is possible to obtain a relative quantity that can be compared between different experiments,[147] whenever the expression of the latter is constant. It is worth pointing out that actin does not always have the desired stability in its gene expression.[148]
    • Health. Some alleles of actin cause diseases; for this reason techniques for their detection have been developed. In addition, actin can be used as an indirect marker in surgical pathology: it is possible to use variations in the pattern of its distribution in tissue as a marker of invasion in neoplasia, vasculitis, and other conditions.[149] Further, due to actin’s close association with the apparatus of muscular contraction its levels in skeletal muscle diminishes when these tissues atrophy, it can therefore be used as a marker of this physiological process.[150]
    • Food technology. It is possible to determine the quality of certain processed foods, such as sausages, by quantifying the amount of actin present in the constituent meat. Traditionally, a method has been used that is based on the detection of 3-methylhistidine in hydrolyzed samples of these products, as this compound is present in actin and F-myosin’s heavy chain (both are major components of muscle). The generation of this compound in flesh derives from the methylation of histidine residues present in both proteins.[151][152]

    Actin is used in scientific and technological laboratories as a track for molecular motors such as myosin (either in muscle tissue or outside it) and as a necessary component for cellular functioning. It can also be used as a diagnostic tool, as several of its anomalous variants are related to the appearance of specific pathologies.


    Bacteria therefore possess a cytoskeleton with homologous elements to actin (for example, MreB, ParM, and MamK), even though the amino acid sequence of these proteins diverges from that present in animal cells. However, MreB and ParM have a high degree of structural similarity to eukaryotic actin. The highly dynamic microfilaments formed by the aggregation of MreB and ParM are essential to cell viability and they are involved in cell morphogenesis, chromosome segregation, and cell polarity. ParM is an actin homologue that is coded in a plasmid and it is involved in the regulation of plasmid DNA.[141][4] ParMs from different bacterial plasmids can form astonishingly diverse helical structures comprising two[142] [143] or four[144] strands to maintain faithful plasmid inheritance.

    The bacterial cytoskeleton may not be as complex as that found in eukaryotes; however, it contains proteins that are highly similar to actin monomers and polymers. The bacterial protein MreB polymerizes into thin non-helical filaments and occasionally into helical structures similar to F-actin.[139][17] Furthermore its crystalline structure is very similar to that of G-actin (in terms of its three-dimensional conformation), there are even similarities between the MreB protofilaments and F-actin. The bacterial cytoskeleton also contains the FtsZ proteins, which are similar to tubulin.[140]

    Equivalents in bacteria

    Some authors point out that the behaviour of actin, tubulin and histone, a protein involved in the stabilization and regulation of DNA, are similar in their ability to bind nucleotides and in their ability of take advantage of Brownian motion. It has also been suggested that they all have a common ancestor.[137] Therefore evolutionary processes resulted in the diversification of ancestral proteins into the varieties present today, conserving, among others, actins as efficient molecules that were able to tackle essential ancestral biological processes, such as endocytosis.[138]

    Structure of MreB, a bacterial protein whose three-dimensional structure resembles that of G-actin.

    The eukaryotic cytoskeleton of organisms among all taxonomic groups have similar components to actin and tubulin. For example, the protein that is coded by the ACTG2 gene in humans is completely equivalent to the homologues present in rats and mice, even though at a nucleotide level the similarity decreases to 92%.[105] However, there are major differences with the equivalents in prokaryotes (FtsZ and MreB), where the similarity between nucleotide sequences is between 40−50 % among different bacteria and archaea species. Some authors suggest that the ancestral protein that gave rise to the model eukaryotic actin resembles the proteins present in modern bacterial cytoskeletons.[136][4]


    The role that actin plays in the invasion process of cancer cells has still not been determined.[135]

    In addition to the previously cited example, actin polymerization is stimulated in the initial steps of the internalization of some viruses, notably HIV, by, for example, inactivating the cofilin complex.[134]

    • Arp2/3 complex, Ena/VASP proteins, cofilin, a buffering protein and nucleation promoters, such as vinculin complex. Through these movements they form protrusions that reach the neighbouring cells, infecting them as well so that the immune system can only fight the infection through cell immunity. The movement could be caused by the modification of the curve and debranching of the filaments.[131] Other species, such as Mycobacterium marinum and Burkholderia pseudomallei, are also capable of localized polymerization of cellular actin to aid their movement through a mechanism that is centered on the Arp2/3 complex. In addition the vaccine virus Vaccinia also uses elements of the actin cytoskeleton for its dissemination.[132]
    • [133]

    Some infectious agents use actin, especially cytoplasmic actin, in their life cycle. Two basic forms are present in bacteria:

    Other pathological mechanisms

    [129] However, although there is no record of any case, it is known that γ-actin is also expressed in skeletal muscles, and although it is present in small quantities,

    [128] Some experiments have suggested that the pathological mechanism for this type of hearing loss relates to the F-actin in the mutations being more sensitive to cofilin than normal.[26]