ACTIN BASED REGULATION OF SMOOTH MUSCLE CONTRACTION

骨骼肌、心肌和平滑肌肉的收缩是由三磷酸腺苷引起的。 肌球蛋白和肌动蛋白相互作用的依赖性。这些是相同的 蛋白质也是几个关键过程所必需的，比如细胞 分裂，在非肌肉细胞中。产生相互作用的力 肌球蛋白和肌球蛋白受肌球蛋白或肌球蛋白变化的调节。 而骨骼肌和心肌主要是通过 肌动蛋白细丝，由原肌球蛋白和肌钙蛋白组成 一直被认为是由磷酸化水平调节的 肌球蛋白。来自几个实验室的证据表明，平滑肌肉 收缩也可能受肌动蛋白结合蛋白的调节。二 与这一活动有关的蛋白质是钙调蛋白和钙蛋白。两者都有 众所周知，蛋白质可以抑制ATP的高水解率 在肌球蛋白和肌动蛋白同时存在的情况下。我们希望能确定 这些蛋白质的作用机制，并特别注意 骨骼肌原肌球蛋白-肌钙蛋白系统与心脏的差异 肌肉。这将通过确定这些蛋白质的效果来实现， 单独和组合，对各种化学物质的结合 肌球蛋白到肌动蛋白的状态。我们还将使用停流动力 确定这些蛋白质对关键转变影响的测量方法 在肌动球蛋白状态之间。我们也希望展示一下 这些蛋白质存在于平滑肌细胞中。监管方面的差异与 骨骼肌和心肌可用于干预 高血压、子宫紊乱、消化紊乱或其他紊乱 涉及到平滑肌肉收缩。

The contraction of skeletal, cardiac and smooth muscles occurs by an ATP dependent interaction of the proteins myosin and actin. These same proteins are also required for several critical processes, such as cell division, in nonmuscle cells. The force producing interaction between actin and myosin is regulated by changes in either myosin or actin. Whereas skeletal and cardiac muscle are regulated primarily through the actin filament, by the proteins tropomyosin and troponin, smooth muscle has been thought to be regulated by the level of phosphorylation of myosin. Evidence from several laboratories suggest that smooth muscle contraction may also be modulated by actin binding proteins. Two proteins implicated in this activity are caldesmon and calponin. Both proteins are known to inhibit the high rate of ATP hydrolysis that occurs in the presence of both myosin and actin. We hope to determine the mechanism by which these proteins function and make particular note of differences with the tropomyosin-troponin system of skeletal and cardiac muscle. This will be done by determining the effect of these proteins, individually and in combination, on the binding of various chemical states of myosin to actin. We will also use stopped flow kinetic measurements to determine the effect of these proteins on key transitions between actomyosin states. We also hope to demonstrate the function of these proteins in smooth muscle cells. Differences in regulation from skeletal and cardiac muscle may be exploited for the intervention of hypertension, uterine disorders, digestive disorders or other disorders involving smooth muscle contraction.