ACTIN-BASED REGULATION OF SMOOTH MUSCLE CONTRACTION

骨骼肌、心肌和平滑肌的收缩是由ATP 肌球蛋白和肌动蛋白的依赖性相互作用。 这些相同 蛋白质还需要几个关键过程，如细胞 分裂，在非肌肉细胞中。 产生相互作用的力 肌动蛋白和肌球蛋白是由肌球蛋白或肌动蛋白的变化来调节的。 而骨骼肌和心肌主要是通过 肌动蛋白丝，由蛋白质原肌球蛋白和肌钙蛋白，平滑肌 被认为是由磷酸化水平调节的， 肌球蛋白 来自多个实验室的证据表明，平滑肌 收缩也可由肌动蛋白结合蛋白调节。 两 参与该活性的蛋白质是钙调蛋白和钙调蛋白。 两 已知蛋白质抑制ATP水解的高速率， 同时存在肌球蛋白和肌动蛋白。 我们希望确定 这些蛋白质的功能机制并特别注意 与骨骼肌和心脏的原肌球蛋白-肌钙蛋白系统的差异 肌肉. 这将通过确定这些蛋白质的作用来完成， 单独和组合，对各种化学品的结合 肌球蛋白转变为肌动蛋白。 我们还将使用停流动力学 测量以确定这些蛋白质对关键转变的影响 在肌动球蛋白状态之间。 我们还希望展示 平滑肌细胞中的这些蛋白质。 监管差异 骨骼肌和心肌可用于干预 高血压、子宫疾病、消化系统疾病或其他疾病 包括平滑肌收缩。

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.