Эукариотикалық жасушалардың цитоплазмасындағы актин жіпшелері

Filament in the cytoplasm of eukaryotic cells

Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other proteins in the cell. Microfilaments are usually about 7 nm in diameter and made up of two strands of actin. Microfilament functions include cytokinesis, amoeboid movement, cell motility, changes in cell shape, endocytosis and exocytosis, cell contractility, and mechanical stability. Microfilaments are flexible and relatively strong, resisting buckling by multi piconewton compressive forces and filament fracture by nanonewton tensile forces. In inducing cell motility, one end of the actin filament elongates while the other end contracts, presumably by myosin II molecular motors. Additionally, they function as part of actomyosin driven contractile molecular motors, wherein the thin filaments serve as tensile platforms for myosin's ATP dependent pulling action in muscle contraction and pseudopod advancement. Microfilaments have a tough, flexible framework which helps the cell in movement. Actin was first discovered in rabbit skeletal muscle in the mid 1940 by F. B. Straub. Almost 20 years later, H. E. Huxley demonstrated that actin is essential for muscle constriction. The mechanism in which actin creates long filaments was first described in the mid 1980. Later studies showed that actin has an important role in cell shape, motility, and cytokinesis.

Actin filaments are assembled in two general types of structures: bundles and networks. Bundles can be composed of polar filament arrays, in which all barbed ends point to the same end of the bundle, or non polar arrays, where the barbed ends point towards both ends. A class of actin binding proteins, called cross linking proteins, dictate the formation of these structures. Cross linking proteins determine filament orientation and spacing in the bundles and networks. These structures are regulated by many other classes of actin binding proteins, including motor proteins, branching proteins, severing proteins, polymerization promoters, and capping proteins.

Measuring approximately 6 nm in diameter, microfilaments are the thinnest fibers of the cytoskeleton. They are polymers of actin subunits (globular actin, or G actin), which as part of the fiber are referred to as filamentous actin, or F actin. Each microfilament is made up of two helical, interlaced strands of subunits. Much like microtubules, actin filaments are polarized. Electron micrographs have provided evidence of their fast growing barbed ends and their slow growing pointed end. This polarity has been determined by the pattern created by the binding of myosin S1 fragments: they themselves are subunits of the larger myosin II protein complex. The pointed end is commonly referred to as the minus (−) end and the barbed end is referred to as the plus (+) end. In vitro actin polymerization, or nucleation, starts with the self association of three G actin monomers to form a trimer. ATP bound actin then itself binds the barbed end, and the ATP is subsequently hydrolyzed. ATP hydrolysis occurs with a half time of about 2 seconds, while the half time for the dissociation of the inorganic phosphate is about 6 minutes.

As a result of ATP hydrolysis, filaments elongate approximately 10 times faster at their barbed ends than their pointed ends. At steady state, the polymerization rate at the barbed end matches the depolymerization rate at the pointed end, and microfilaments are said to be treadmilling. Treadmilling results in elongation in the barbed end and shortening in the pointed end, so that the filament in total moves. Since both processes are energetically favorable, this means force is generated, the energy ultimately coming from ATP. Specialized unique actin cytoskeletal structures are found adjacent to the plasma membrane. Four remarkable examples include red blood cells, human embryonic kidney cells, neurons, and sperm cells. In red blood cells, a spectrin actin hexagonal lattice is formed by interconnected short actin filaments. In human embryonic kidney cells, the cortical actin forms a scale free fractal structure. First found in neuronal axons, actin forms periodic rings that are stabilized by spectrin and adducin and this ring structure was then found by He et al 2016 to occur in almost every neuronal type and glial cells, across seemingly every animal taxon including Caenorhabditis elegans, Drosophila, Gallus gallus and Mus musculus. And in mammalian sperm, actin forms a helical structure in the midpiece, i. e., the first segment of the flagellum.

Myosin motors are intracellular ATP dependent enzymes that bind to and move along actin filaments. Various classes of myosin motors have very different behaviors, including exerting tension in the cell and transporting cargo vesicles.

One proposed model suggests the existence of actin filament barbed end tracking molecular motors termed "actoclampin". The proposed actoclampins generate the propulsive forces needed for actin based motility of lamellipodia, filopodia, invadipodia, dendritic spines, intracellular vesicles, and motile processes in endocytosis, exocytosis, podosome formation, and phagocytosis. Actoclampin motors also propel such intracellular pathogens as Listeria monocytogenes, Shigella flexneri, Vaccinia and Rickettsia. When assembled under suitable conditions, these end tracking molecular motors can also propel biomimetic particles. The term actoclampin is derived from acto to indicate the involvement of an actin filament, as in actomyosin, and clamp to indicate a clasping device used for strengthening flexible/moving objects and for securely fastening two or more components, followed by the suffix in to indicate its protein origin. An actin filament end tracking protein may thus be termed a clampin. Dickinson and Purich recognized that prompt ATP hydrolysis could explain the forces achieved during actin based motility. The term actoclampin is generic and applies to all actin filament end tracking molecular motors, irrespective of whether they are driven actively by an ATP activated mechanism or passively. Some actoclampins (e. g., those involving Ena/VASP proteins, WASP, and N WASP) apparently require Arp2/3 mediated filament initiation to form the actin polymerization nucleus that is then "loaded" onto the end tracker before processive motility can commence. To generate a new filament, Arp2/3 requires a "mother" filament, monomeric ATP actin, and an activating domain from Listeria ActA or the VCA region of N WASP. The Arp2/3 complex binds to the side of the mother filament, forming a Y shaped branch having a 70 degree angle with respect to the longitudinal axis of the mother filament. Then upon activation by ActA or VCA, the Arp complex is believed to undergo a major conformational change, bringing its two actin related protein subunits near enough to each other to generate a new filament gate. Whether ATP hydrolysis may be required for nucleation and/or Y branch release is a matter under active investigation.