Tropomyosin muscle physiology

Study of the molecular biology of calcium regulation of muscle contraction was initiated by the discovery of a new protein factor sensitizing actomyosin to calcium ions (Ebashi, 1963 Ebashi and Ebashi, 1964). This protein factor was called native tropomyosin, because of its similarity in amino acid composition to tropomyosin, which had been discovered earlier (Bailey, 1946, 1948). It was soon found that this factor is a complex of tropomyosin and a new globular protein, termed troponin (Ebashi and Kodama, 1965 Ebashi et al., 1968). Thus four proteins, i.e., myosin, actin, troponin, and tropomyosin, are involved in calcium-regulated physiological muscle contraction (Ebashi et al., 1968, 1969 Ebashi and Endo, 1968). The contractile interaction between myosin and actin is depressed by troponin and tropomyosin in the absence of calcium ions. When calcium ion acts on troponin, this depression is removed and the contractile interaction is then activated (Figs. 1 and 2). 

The SDS-gel electrophoretic pattern of tropomyosin showed two bands, designated a and /8, around 35,000 Da (Cummins and Perry, 1973). The ratio of the two subunits varied from tissue to tissue mostly a subunit in fast skeletal muscle, equimolar a and )8 subunits in slow skeletal muscle, and exclusively a subunit in cardiac muscle (Bronson and Schachat, 1982). The tropomyosin molecule consists of aa or ajS dimers. A )8/8 molecule produced in vitro showed the same Ca -sensitizing action as that of aj8- or aa-tropomyosin (Cummins and Perry, 1973). Hence physiologically both a and /3 subunits are identical. 

In this section, properties of calcium regulatory proteins from vertebrate skeletal muscle were reviewed with particular reference to the physiological structure and function that have been the major interest since the discovery of native tropomyosin. 

As the name implies, smooth muscle lacks the highly ordered sarcomere structure of striated muscle, having thick and thin filaments in less orderly arrays with relatively less myosin (one fifth as much) than in striated muscle. Smooth muscle thin filaments have tropomyosin but generally lack troponin. Myosin in smooth muscle is found in monomeric form as well as small thick filaments, and phosphorylation is almost essential for condensation of monomeric myosin into filaments. Thus, the amount of myosin available to cross-bridge with actin may be physiologically adjustable. Like other myosin II types, smooth muscle myosin is a hexamer, and several isoforms of the heavy chains and both light chains are known. The SM-1 isoform (M.W. 204,000) has an unusually long COOH-... 

In vitro experimentation has shown that caldesmon is an integral component of smooth muscle thin filaments and plays a central role in their Ca2+-dependent regulation. A mechanism analogous to that of troponin has been proposed this now requires extensive testing. The structure of the regulatory domain of caldesmon is not well defined and we look forward to being able to describe this in three dimensions and in combination with its physiological partners actin, tropomyosin, and calmodulin. 

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