Role of Unconventional Myosin Myo1c in Cell Motility

描述(由申请人提供)： 肌球蛋白是一种分子马达，它利用三磷酸腺苷水解产生的能量来调节基于肌动蛋白的运动。肌球蛋白的缺陷会导致心肌病、神经问题、耳聋和失明。I类肌球蛋白是一种小的、单头的、非丝状的蛋白质，与细胞运动、极性的建立和肌动蛋白的组织有关。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。具体地说，第一个目标是研究内源性和表达的Myo1c在固定的和活的组织培养细胞中的定位，并确定在动态细胞骨架事件中它集中在哪里。在第二个目标中，将监测降低Myo1c细胞浓度对细胞骨架特性和细胞运动的影响。作为补充，在第三个目标中，将研究增加Myo1c或突变的Myo1c的细胞浓度对相同的细胞骨架和运动特性的影响。这些实验将检验这样的假设，即Myo1c集中在经历细胞骨架快速重排的细胞区域，并在细胞皮质调节动态细胞骨架事件。

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.