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[[Image:Actin_with_ADP_highlighted.png|thumb|G-Actin ([[Protein_Data_Bank|PDB]] code: 1j6z). [[adenosine triphosphate|ADP]] and the divalent cation are highlighted.]]
[[Image:Actin_filament_atomic_model.png|thumb|F-Actin; surface representation of 13 subunit repeat based on Ken Holmes' actin filament model]]

'''Actin''' is a globular, roughly 42-kDa [[protein]] found in all [[Eukaryote|eukaryotic cells]] (except for [[nematode]] sperm) where it may be present at concentrations of over 100 μM. It is also one of the most highly-[[Conservation (genetics)|conserved]] proteins, differing by no more than 20% in [[species]] as diverse as [[algae]] and [[human]]s. It is the [[monomer]]ic subunit of [[microfilaments]], one of the three major components of the [[cytoskeleton]], and of '''thin filaments''', which are part of the contractile apparatus in muscle cells. Thus, actin participates in many important cellular functions, including [[#Actomyosin filaments|muscle contraction]], cell [[motility]], cell division and [[cytokinesis]], vesicle and organelle movement, [[cell signaling]], and the establishment and maintenance of [[cell junction]]s and cell shape.

==Formation of thin filament==
[[Image:Thin filament formation.svg|thumb|500px|center|Formation of thin filament]]

==Genetics==
[[Image:Adherens Junctions structural proteins.svg|thumb|350px|]]Principal interactions of structural proteins at [[cadherin]]-based adherens junction. Actin filaments are linked to α-actinin and to membrane through [[vinculin]]. The head domain of vinculin associates to E-cadherin via α-, β-, and γ-catenins. The tail domain of vinculin binds to membrane lipids and to actin filaments.
The protein actin is one of the most highly conserved throughout evolution because it interacts with a large number of other proteins, with 80.2% sequence [[Conservation (genetics)|conservation]] at the [[gene]] level between ''[[Human|Homo sapiens]]'' and ''[[Saccharomyces cerevisiae]]'' (a species of yeast), and 95% conservation of the [[primary structure]] of the protein product. 

Although most [[yeast]]s have only a single actin gene, higher [[eukaryote]]s, in general, [[gene expression|express]] several [[isoform]]s of actin encoded by a family of related genes. [[Mammal]]s have at least six actin isoforms coded by separate genes,<ref name="Vandekerckhove J. and Weber K.">Vandekerckhove J. and Weber K. (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|J Mol Biol]] 126:783–802 {{Entrez Pubmed|745245}}</ref> which are divided into three classes (alpha, [[Beta-actin|beta]] and gamma) according to their [[isoelectric point]]. 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]]''.<ref name="Khaitlina SY">Khaitlina SY (2001) Functional specificity of actin isoforms. [[International Review of Cytology|Int Rev Cytol]] 202:35-98 {{Entrez Pubmed|11061563}}</ref>

The typical actin gene has an approximately 100-nucleotide [[5' UTR]], a 1200-nucleotide [[Translation (genetics)|translated]] region, and a 200-nucleotide [[3' UTR]]. The majority of actin genes are interrupted by [[intron]]s, with up to 6 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 [[prokaryote]]s appear to possess genes such as [[MreB]], which encode [[homology (biology)|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 polymerised form is [[Microtubule#Dynamic Instability|dynamically unstable]], and appears to partition the plasmid [[DNA]] into the daughter cells during cell division by a mechanism analogous to that employed by microtubules in eukaryotic [[mitosis]].<ref name=" Garner EC et al"> Garner EC et al (2007) Reconstitution of DNA segregation driven by assembly of a prokaryotic actin homolog. [[Science (journal)|Science]] 315:1270-1274 {{Entrez Pubmed|17332412}}</ref>
Actin is found in both smooth and rough endoplasmic reticulums.

==Functions==
Actin has three main functions in cells :
* To form the most dynamic one of the three subclasses of the [[cytoskeleton]], which gives mechanical support to cells, and hardwires the cytoplasm with the surroundings to support signal transduction.
* To allow [[cell motility]] (see [[Microfilament#Microfilament-based motility by actoclampin molecular motors|Actoclampin molecular motors]]).
* In [[muscle]] cells as well as non-muscle cells, to generate force together with [[myosin]] proteins to support muscle contraction, [[Vesicle (biology)|vesicle]] movement, and other transport processes.

===[[Microfilaments]]===
Individual [[subunit]]s of actin are known as [[Globular protein|globular]] actin (G-actin). G-actin subunits assemble into long filamentous [[Biopolymer|polymer]]s called F-actin. Two parallel F-actin strands twist around each other in a helical formation, giving rise to microfilaments of the cytoskeleton. Microfilaments measure approximately 7 [[nanometer|nm]] in [[diameter]] with a loop of the helix repeating every 37 nm.

====Polarity====
The polarity of an actin filament can be determined by decorating the microfilament with [[myosin]] "S1" fragments, creating barbed (+) and pointed (-) ends on the filament. An S1 fragment is composed of the head and neck domains of myosin II.

===Actomyosin filaments===
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 [[myofibril]]s. These fibrils comprise the mechanism of [[muscle contraction]]. Using the hydrolysis of [[Adenosine triphosphate|ATP]] for energy, myosin heads undergo a cycle during which they attach to thin filaments, exerting a tension, and then depending on the load, perform a power stroke that causes the thin filaments to slide past, shortening the muscle.

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.

Actin polymerization and depolymerization is necessary in [[chemotaxis]] and [[cytokinesis]].  Nucleating factors are necessary to stimulate actin polymerization.  Also, Actin filaments themselves bind ATP, and hydrolysis of this ATP stimulates destabilization of the polymer.

==History==
Actin was first observed [[experiment]]ally in [[1887]] by W.D. Halliburton, who extracted a protein from muscle that 'coagulated' preparations of myosin, and that he dubbed "myosin-ferment."<ref name="Halliburton">Halliburton, W.D. (1887) On muscle plasma. J. Physiol. 8, 133</ref> However, Halliburton was unable to further characterise his findings, and the discovery of actin is credited instead to Brúnó F. 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 extracting muscle protein that allowed him to isolate substantial amounts of relatively-pure actin. Straub's method is essentially the same as that used in laboratories today. Szent-Gyorgyi had previously described the more viscous form of myosin produced by slow muscle extractions as 'activated' myosin, and, since Straub's protein produced the activating effect, it was dubbed ''actin''. The hostilities of [[World War II]] meant that Szent-Gyorgyi and Straub were unable to publish the work in [[Western countries|Western]] [[scientific journal]]s; it became well-known in the West only in [[1945]], when it was published as a supplement to the Acta Physiologica Scandinavica.<ref name="Szent_Gyorgyi">Szent-Gyorgyi, A. (1945) Studies on muscle. Acta Physiol Scandinav 9 (suppl. 25)</ref>

Straub continued to work on actin and in [[1950]] reported that actin contains bound [[adenosine triphosphate|ATP]] <ref name="Straub">Straub, F.B. and Feuer, G. (1950) Adenosinetriphosphate the functional group of actin. Biochim. Biophys. Acta. 4, 455-470 {{Entrez Pubmed|2673365}}</ref> and that, during polymerisation of the protein into microfilaments, the [[nucleotide]] is hydrolysed to [[adenosine diphosphate|ADP]] and inorganic [[phosphate]] (which remain bound in 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]].<ref name="Bárány">Bárány, M., Barron, J.T., Gu, L., and Bárány, K. (2001) Exchange of the actin-bound nucleotide in intact arterial smooth muscle. [[Journal of Biological Chemistry|J. Biol. Chem.]], 276, 48398-48403 {{Entrez Pubmed|11602582}}</ref>

The [[X-ray crystallography|crystal structure]] of G-actin was solved in [[1990]] by Kabsch and colleagues.<ref name="Kabsch">Kabsch, W., Mannherz, E.G., Suck, D., Pai, E.F., and Holmes, K.C. (1990) Atomic structure of the actin:DNase I complex. [[Nature (journal)|Nature]], 347, 37-44 {{Entrez Pubmed|2395459}}</ref> In the same year a model for F-actin was proposed by Holmes and colleagues.<ref name="Holmes">Holmes KC, Popp D, Gebhard W, Kabsch W. (1990) Atomic model of the actin filament. [[Nature (journal)|Nature]], 347, 21-2 {{Entrez Pubmed|2395461}}</ref> The model was derived by fitting a helix of G-actin structures according to low-resolution fiber diffraction data from the filament. Several models of the filament have been proposed since. However there is still no high-resolution X-ray structure of F-actin.

The [[Listeria]] bacteria use the cellular machinery to move around inside the host cell, by inducing directed polymerisation of actin by the [[ActA]] [[transmembrane protein]], thus pushing the bacterial cell around.

==See also==
*[[MreB]] - an actin homologue in bacteria
*[[Motor protein]]
*[[ACTA1]] - alpha actin 1
*[[ACTB]] - beta actin
*[[ACTG1]] - gamma actin 1

==References==
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{{Cytoskeletal Proteins}}
{{Muscle tissue}}
{{Autoantigens}}

[[Category:Cytoskeleton]]
[[Category:Structural proteins]]
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