CALPONIN--ITS ROLE IN SMOOTH MUSCLE REGULATION

这个子项目的长期目标是破译 钙蛋白(CAP)在调节平滑肌收缩中的作用。这个 CAP的生化特性强烈表明，它可以调节 通过改变肌动蛋白之间的相互作用来调节平滑肌的收缩能力 还有肌球蛋白。使用外源添加的盖子或盖子的实验结果 敌手似乎支持这一观点。另一方面，就地 本地化研究表明，Cap主要局限于 细胞骨架，而不是鸡肌胃细胞的肌动蛋白区域。 这些发现提出了几种可能性：1)CAP定位于 肌动球蛋白区域处于松弛状态，其功能是通过抑制 肌动蛋白-肌球蛋白相互作用；在刺激下，它迁移出 肌动球蛋白区域到细胞骨架区域。2)CAP未本地化于 肌动球蛋白区域与收缩状态和组织类型无关； 相反，它被定位在细胞骨架区域，在那里它进行调节 通过细胞骨架的收缩。3)CAP不参与 可缩性。在这个过程中，我们将通过以下方式测试这些可能性 进行了以下实验：1)现场测定 帽的定位作为收缩状态和细胞类型的函数。2) 测定头孢菌素及其各种收缩和收缩的体内化学计量学 细胞骨架蛋白。3)研究了CAP与各种因素之间的相互作用 平滑肌肉蛋白。4)确定封顶和封顶的效果 拮抗剂对Smooth收缩能力和细胞骨架结构的影响 肌肉细胞。从这个项目中得出的结果可能会揭示真实的 帽的生理功能和揭示平滑肌中的新概念 生理学，如细胞骨架与收缩的关系。

The long term objective of this subproject is to decipher the role of calponin (CaP) in the regulation of smooth muscle contraction. The biochemical properties of CaP strongly suggest that it can regulate the contractility of smooth muscle by modifying the interaction between actin and myosin. Results of experiments using exogenously added CaP or CaP antagonist seem to support this notion. On the other hand, in situ localization studies show that Cap is primarily localized in the cytoskeletal rather than the actomyosin regions of chicken gizzard cells. These findings suggest several possibilities: 1) CaP is localized in the actomyosin regions in the relaxed state where it functions by inhibiting actin-myosin interaction; upon stimulation it migrates out of the actomyosin regions to the cytoskeletal regions. 2) CaP is not localized in the actomyosin regions regardless of contractile state and type of tissue; instead, it is localized in the cytoskeletal regions where it modulates contractibility via the cytoskeleton. 3) CaP is not involved in contractibility. In this process we will test these possibilities by carrying out the following experiments: 1) Determine the in situ localization of CaP as a function of contractile state and cell type. 2) Determine the in vivo stoichiometries of CaP and various contractile and cytoskeletal proteins. 3) Study the interaction between CaP and various smooth muscle proteins. 4) Determine the effects of CaP and CaP antagonists on the contractility and cytoskeletal structure of smooth muscle cells. Results derived from this project may reveal the true physiological function of CaP and uncover novel concepts in smooth muscle physiology such as the involvement of the cytoskeleton in contractility.