Actin-myosin interaction regulators

Table 49—7 summarizes and compares the regulation of actin-myosin interactions (activation of myosin ATPase) in striated and smooth muscles. 

Tropomyosin and troponin are proteins located in the thin filaments, and together with Ca2+, they regulate the interaction of actin and myosin (Fig. 43-3) [5]. Tropomyosin is an a-helical protein consisting of two polypeptide chains its structure is similar to that of the rod portion of myosin. Troponin is a complex of three proteins. If the tropomyosin-troponin complex is present, actin cannot stimulate the ATPase activity of myosin unless the concentration of free Ca2+ increases substantially, while a system consisting solely of purified actin and myosin does not exhibit any Ca2+ dependence. Thus, the actin-myosin interaction is controlled by Ca2+ in the presence of the regulatory troponin-tropomyosin complex [6]. 

Figure 22.12 Regulation of actin-myosin interaction in smooth muscle via the light-chain kinase and phosphatase and effect on blood pressure. ions bind to calmodulin and the complex stimulates the conversion of inactive myosin light chain kinase (MLCK) to active MLCK which then phosphorylates the light chain. This results in activation of the cross-bridge cycle. The overall effect is vasoconstriction of the arteriole, which increases blood pressure.

The muscle sarcomere contains the principal contractile proteins myosin and actin (Fig. 3A to C), which on their own can produce force and movement, together with a number of cytoskeletal and regulatory proteins. The latter include titin, C-protein (MyBP-C), tropomyosin, troponin, a-actinin, myomesin, M-protein, and so on. Some of these help to organize the myosin and actin filaments in the sarcomere, some to define the filament lengths and structure, some to regulate activity, and some to modulate the actin-myosin interaction when the muscle is active. 

Troponin Troponin C Troponin I Troponin T 70 18 21 31 5 I band Ca regulation Ca binding Inhibition of actin-myosin interaction Binding to tropomyosin... 

Actin is present in all eukaryotic cells where it has structural and mobility functions. Most movement associated with microfilaments requires myosin. The myosin-to-actin ratio is much lower in nonmuscle cells, and myosin bundles are much smaller (10-20 molecules rather than about 500), but the interaction between myosin and actin in nonmuscle cells is generally similar to that in muscle. As in smooth muscle, myosin aggregation and activation of the actin-myosin interaction are regulated primarily by light chain phosphorylation. Myosins involved in transporting organelles along actin filaments are often activated by Ca-CaM. 

The regulation of actin myosin interaction by phosphorylation has been characterised in vitro, and the main process that is influenced by phosphorylation appears to be a step associated with the Pi release (Sellers et al. 1982, Sellers 1985, Greene and Sellers 1987). Increased levels of Ca and phosphorylation increase active force in muscle fibres which could be consistent with an influence of phosphorylation on the P, release reaction. By analogy with an analysis proposed for the events associated with force... 

Sobieszek A, Small JV (1977) Regulation of the actin-myosin interaction in vertebrate smooth muscle activation via a myosin light-chain kinase and the effect of tropomyosin. J Molec Biol 112 559-576... 

Sobue K, Takahashi K, Wakabayashi 1 (1985) CaldesmonlSO regulates the tropomyosin-enhanced actin-myosin interaction in gizzard smooth muscle. Biochem Biophys Res Commun 132 645-651... 

Adelstein, R.S. Eisenberg, E. (1980). Regulation and kinetics of the actin-myosin-ATP interaction. Ann. Rev. Biochem. 49,921-956. 

Figure 49-14. Regulation of smooth muscle contraction by Ca. pL-myosin is the phosphorylated light chain of myosin L-myosin is the dephosphorylated light chain. (Adapted from Adelstein RS, Eisenberg R Regulation and kinetics of actin-myosin ATP interaction. Annu Rev Biochem 1980 49 921.)...

Current studies suggest a vital role for CaD in the regulation of smooth muscle contraction since it inhibits the actin-activated ATPase activity of myosin (Da-browska et al., 1985 Smith and Marston, 1985 Moody et al., 1985 Sobue et al., 1985) and its subfragments (Lash et al., 1986 Chalovich et al., 1987). However, defining the precise role of CaD in cells requires an understanding of its interaction with several key proteins, namely, actin, myosin, calmodulin, and caltropin. 

The major relaxing transmitters are those that elevate the cAMP or cGMP concentration (Fig. 3). Adenosine stimulates the activity of cAMP kinase. The next step is not clear, but evidence has been accumulated that cAMP kinase decreases the calcium sensitivity of the contractile machinery. In vitro, cAMP kinase phosphorylated MLCK and decreased thereby the affinity of MLCK for calcium-calmodulin. However, this regulation does not occur in intact smooth muscle. Possible other substrate candidates for cAMP kinase are the heat stable protein HSP 20, (A heat stable protein of 20 kDa that is phosphorylated by cGMP kinase. It has been postulated that phospho-HSP 20 interferes with the interaction between actin and myosin allowing thereby smooth muscle relaxation without dephosphorylation of the rMLC.) Rho A and MLCP that are phosphorylated also by cGMP kinase I (Fig. 3). 

Troponins T or I Proteins found predominantly in cardiac muscle that regulate calcium-mediated interaction of actin and myosin troponins I and T are released into the blood from myocytes at the time of myocardial cell necrosis after infarction. These biochemical markers become elevated and are used in the diagnosis of myocardial infarction. 

Troponin C Regulates muscle contraction complex formation triggers actin to realign and interact with myosin (389,390) — inhibited by relaxins, which are themselves Ca2+-binding proteins (v.s.)... 

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