Actin

Actin is a protein directly involved in the conversion of chemical energy into mechanical work. It contains ATP as an essential component of the molecule (Szent-Gyorgyi and Prior 1966; Bárány et al. 1961). Actin's interaction with myosin results in muscular contraction. Although muscle actin has been the most studied, the protein is widely found in nature and is perhaps a structural component of all cell types. Actin is believed to be involved in cytoplasmic streaming and cell locomotion (Palevitz et al. 1974) (Lazarides and Weber 1974). See also: Matsutake et al. (1975), Yang and Perdue (1972), Orr et al. (1972), Spooner et al. (1971), Wessells et al. (1971), Pollard et al. (1970), Weihing and Korn (1969). Nachmias and Huxley (1970) report on actin from slime mold and hypothesize that muscle contraction may have evolved from cytoplasmic streaming. Gabbiani et al. (1975) speculate that the increased contractile protein of cancer cells is related to their increased motility and invasiveness. Weihing and Korn (1971) report that amoeba actin reacts with rabbit muscle myosin. See also Kersey et al. (1976).

Actin, a key component of muscle myofibrils, is characterized by its capacity to combine with the heavy-meromyosin (HMM) portion of the myosin filament to form the highly viscous actomyosin (Ishikawa et al. 1969). See also Marston and Weber (1975) and Mulhern et al. (1975). Myofibrils, functional units of muscle cells, contain two types of partially overlapping longitudinal filaments, actin and myosin, in definite array. Myosin has ATPase sites along the filament surface at the thicker, HMM end of the molecule. Muscular contraction occurs through a sliding toward the center of the sacromere, of actin filaments along adjacent myosin filaments with the accompaniment of linkages between the two. Myofibrils shorten, although the actin and myosin molecules do not. Muscular tension is maintained by forces between adjacent filaments. It is the HMM portion of myosin that possesses ATPase activity (Szent-Gyorgyi 1953) and the sites that combine with actin.

Finlayson et al. (1969) have reported on the actin-myosin interaction. They indicate that myosin molecules are bound independently at sites on F-actin. Each site consists of two G-actin units.

Actin is characterized by its superprecipitation with myosin, its activation of myosin ATPase (EC 3.6.1.3) at low ionic strength, and its depolymerization, i.e., loss of viscosity, on adding ATP at high ionic strength. The reversible polymerization is an important property for its purification. Actin is usually isolated as a soluble globulin monomer, G-actin, which may be reversibly transformed into a viscous polymerized fibrous form, F-actin, by the addition of neutral salts and at neutral or slightly alkaline pH. See also Chantler and Gratzer (1975). The reaction, which involves bound nucleotide is:

Depolymerization is only possible in the presence of ATP (Szent-Gyorgyi and Prior 1966; Mommaerts 1951). See also: Arisaka et al. (1975), Mannherz et al. (1975) and Tawada and Oosawa (1969). Martonosi and Gouvea (1961) have shown that inosine 5'-triphosphate can replace ATP without affecting the polymerizability of G-actin. The removal by charcoal of bound ATP prevents: 1) G-actin from polymerizing; 2) formation of actomyosin at elevated ionic strength; and 3) the activation of myosin ATPase activity at low ionic strength (Bárány et al. 1961). The G-F transformation per se probably does not participate in muscle contraction (Asakura et al. 1963).

The actin and myosin complex (actomyosin) is dissociated in 0.6 M KCl on addition of ATP (Maruyama and Gergely 1962).

Actin in muscle is closely associated with tropomyosin (Longley 1975; Loscalzo et al. 1975). It has been hypothesized that tropomyosin regulates the structure of actin and controls its interaction with myosin (Tanaka and Oosawa 1971). See also Martonosi (1962) and Drabikowski and Gergely (1962). The thin filament of myofibrils consists of actin monomers in an ≥-helix. It has been suggested that tropomyosin lies in the two grooves of the ≥-helix and at spaced intervals has a troponin molecule. The latter regulates the state of F-actin in response to the binding of calcium ions by troponin. At Ca²⁺ concentration below 10^-8 M, actin is unable to associate the myosin and the muscle is at rest. Upon activation, Ca²⁺ level rises to >10^-5 M and contraction occurs (Lowey 1972). See also Podolsky and Constantin (1964).

According to Lazarides and Lindberg (1974) actin is an inhibitor of deoxyribonuclease I (3 ≥g of actin inhibits 1 ≥g of DNase I) and may control DNase I nucleolytic activity during the cell cycle. See also Schafer et al. (1975) and Mannherz et al. (1975).

Clarke and Masters (1975) and Arnold and Pette (1975) report on the adsorption of glycolytic enzymes to F-actin. It is indicated that actin may have a role in cell metabolism regulation. See also Dedman et al. (1975). Laki and Muszbek (1974) have studied the interaction of F-actin and fibrin which may relate to blood-clot retraction.

The amino acid sequence of rabbit muscle actin has been reported by Elzinga and Collins (1975), Kuehl, Conti and Adelstein (1975) and Elzinga et al. (1973). Electron microscopy of actin has been reviewed by Finch (1975).