Caldesmon actomyosin ATPase activity inhibition

Possible caldesmon-induced movement of tropomyosin away from this site or competition with tropomyosin for the site may prevent potentiation from occurring. The work of Chacko and associates (Horiuchi and Chacko, 1989 Horiuchi et al., 1991), in fact, implies that caldesmon may modulate the magnitude of tropomyosin activation, and therefore may control actomyosin ATPase by inhibiting tropomyosin potentiation. This view would explain how a single caldesmon molecule could influence the reactivity of many actin molecules along thin filaments. Such a mechanism of modulation implies that caldesmon may fine-tune contractile activity but not act as an on-off switch per se. This view also fits with results of the elegant experiments of Fay and his collaborators (Itoh et al., 1989), who showed that myosin phosphoryla-... 

When purified CaD binds to actin-tropomyosin, it inhibits actomyosin ATPase activity. CaM in the presence of Ca + can reverse caldesmon s inhibition of the actin-activated myosin ATPase. However, the affinity of CaM for CaD is rather low (Kgg = 1Q6 M i), with the result that a large molar excess of CaM ( 25-fold) at 25°C in 60 mM KCl is required to reverse caldesmon s inhibition (Pritchard and Mar-ston, 1989 Shirinsky et al, 1988). On the other hand, CaT in the presence of 0.2 mM Ca + is very effective in releasing caldesmon s inhibition at 25°C. Complete recovery in the ATPase rate is achieved when 1 mol of CaT is added per mol of CaD (Mani etal, 1992). In fact, most of the inhibition was released (—90%) by the time... 

Chalovich JM, Cornelius P, Benson CE (1987) Caldesmon inhibits skeletal actomyosin subfragment-1 ATPase activity and the binding of myosin subfragment-1 to actin. J Biol Chem 262 57115716... 

To account for activation of arterial smooth muscle independently of LC20 phosphorylation, attention has been focused on the possible roles of the thin filament-associated regulatory proteins, caldesmon and calponin. Both proteins have been localized in the actomyosin domain of the smooth muscle cell and both have been shown to inhibit actin-activated myosin ATPase by interacting with F-actin, tropomyosin, and/or myosin (Clark et al., 1986 Takahashi et al.,... 

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