Caldesmon and thin-filament regulation of muscle contraction

Abstract

Smooth muscle contraction is regulated by phosphorylation of myosin and also possibly by the actin associated protein, caldesmon. The properties of caldesmon are discussed and compared with those of tropomyosin-troponin, the well characterized actin-based regulatory system of striated muscle. Caldesmon functions quite differently from tropomyosin-troponin. Under relaxing conditions tropomyosin-troponin does not affect the binding of myosin subfragment-1 to actin. In contrast, caldesmon strongly inhibits the binding of subfragment-1 to actin in the presence of ATP. This inhibition of binding parallels the decrease in ATPase activity that occurs as the caldesmon concentration is increased. Caldesmon has the opposite effect on the two headed myosin subfragment, heavy meromyosin. The apparent binding of skeletal heavy meromyosin increases slightly as the caldesmon concentration is increased, although the rate of ATP hydrolysis is inhibited. It is suggested that in the presence of caldesmon, myosin·ATP does not bind to the productive actin binding site but interacts with a distinct site on actin-caldesmon. This could lead to both an inhibition of ATP hydrolysis and an inrease in resting stiffness of relaxed smooth muscle.