Everything about Actin totally explained
Actin is a globular, roughly 42-kDa
protein found in all
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-
conserved proteins, differing by no more than 20% in
species as diverse as
algae and
humans. It is the
monomeric 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
muscle contraction, cell
motility, cell division and
cytokinesis, vesicle and organelle movement,
cell signaling, and the establishment and maintenance of
cell junctions and cell shape.
Formation of thin filament
Genetics
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 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.
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, which are divided into three classes (alpha,
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 can't completely substitute for one another
in vivo.
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 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
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 polymerised form is
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.
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 Actoclampin molecular motors).
- In muscle cells as well as non-muscle cells, to generate force together with myosin proteins to support muscle contraction, vesicle movement, and other transport processes.
Individual
subunits of actin are known as
globular actin (G-actin). G-actin subunits assemble into long filamentous
polymers 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
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
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, 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
experimentally in
1887 by W.D. Halliburton, who extracted a protein from muscle that 'coagulated' preparations of myosin, and that he dubbed "myosin-ferment." 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 scientific journals; it became well-known in the West only in
1945, when it was published as a supplement to the Acta Physiologica Scandinavica.
Straub continued to work on actin and in
1950 reported that actin contains bound
ATP and that, during polymerisation of the protein into microfilaments, the
nucleotide is hydrolysed to
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 wasn't supported through experimentation until
2001.
The
crystal structure of G-actin was solved in
1990 by Kabsch and colleagues. In the same year a model for F-actin was proposed by Holmes and colleagues. 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's 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.
Further Information
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