Role of Unconventional Myosin Myo1c in Cell Motility

描述（由申请人提供）： 肌球蛋白是利用ATP水解产生的能量来介导肌动蛋白运动的分子马达。肌球蛋白的缺陷导致心肌病、神经问题、耳聋和失明。I类肌球蛋白是小的、单头的、非丝状的蛋白质，其与细胞运动、极性的建立和肌动蛋白组织有关。该项目的长期目标是确定一种特定的I类肌球蛋白Myo1c的细胞功能。具体而言，第一个目的是研究固定和活组织培养细胞中内源性和表达的Myo1c的定位，并确定其在动态细胞骨架事件中的集中位置。在第二个目标中，将监测敲低Myo1c的细胞浓度对细胞骨架性质和细胞运动的影响。作为补充方法，将在第三个目标中研究增加Myo1c或突变Myo1c的细胞浓度对相同细胞骨架和运动特征的影响。这些实验将测试的假设，Myo1c集中在细胞区域进行快速重排的细胞骨架和介导的动态细胞骨架事件在细胞皮层。

DESCRIPTION (provided by applicant): Myosins are molecular motors that use the energy derived from ATP hydrolysis to mediate actin-based motility. Defects in myosins result in cardiomyopathies, neurological problems, deafness and blindness. Class I myosins are small, single-headed, non-filamentous proteins that have been implicated in cell motility, establishment of polarity, and actin organization. The long-term objective of this project is to determine the cellular function of one particular class I myosin, Myo1c. Specifically, the first aim is to study the localization of endogenous and expressed Myo1c in fixed and live tissue culture cells, and determine where it concentrates during dynamic cytoskeletal events. In the second aim, the effect of knocking down the cellular concentration of Myo1c on cytoskeletal properties and cell movement will be monitored. As a complementary approach, the effect of increasing the cellular concentration of Myo1c or mutated Myo1c on the same cytoskeletal and motile characteristics will be investigated in the third aim. These experiments will test the hypotheses that Myo1c concentrates in cellular regions undergoing rapid rearrangements of the cytoskeleton and mediates dynamic cytoskeletal events at the cell cortex.