Phosphorylation of Myo1c by cAMP-Dependent Kinase

cAMP 依赖性激酶对 Myo1c 进行磷酸化

• 批准号: 7056295
• 负责人: EMILIE D MILLER
• 金额: $ 4.08万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7056295
• 关键词: actins; cyclic AMP; ear hair cell; enzyme activity; genetic transduction; immunoprecipitation; intracellular transport; laboratory mouse; myosins; phosphorylation; predoctoral investigator; protein kinase A; protein structure function; transport proteins

DESCRIPTION (provided by applicant): Hearing loss and vestibular deficiencies frequently are the result of genetic defects of environmental damage targeting the hair cells in the inner ear. The apical hair cell is composed of actin-filled stereocilia, within which the transduction channels are housed. Myosin 1c (Myo1c), has been identified as an adaptation motor near the tips of the stereocilia. Tip-links connect each stereocilia to its next tallest neighbor and tip-link tension influences the transduction channel open state. Myo1c's role is to reset channel open probability through modulating resting tension of the tip-link following deflection of the hair bundle. The drive of this study is to understand the influence of Protein Kinase A (PKA) phosphorylation on the ability of Myo1c to regulate transduction force production, and open probability. PKA phosphorylation of Myo1c is likely to affect the function of Myo1c, due to the target site's location at a proposed flexible region of the myosin. A change in Myo1c dynamics is likely to have major consequences for transduction open probability in the hair cell. Using biochemical characterization, including in vitro motility and ATPase assays, and immunoprecipitation of Myo1c, the importance of PKA phosphorylation of Myo1c will be determined.

描述（由申请人提供）：听力损失和前庭缺陷通常是针对内耳毛细胞的环境损害的遗传缺陷的结果。顶端毛细胞由充满肌动蛋白的静纤毛组成，其中装有转导通道。肌球蛋白 1c (Myo1c) 已被确定为靠近静纤毛尖端的适应运动。尖端链接将每个静纤毛与其下一个最高的邻居连接，并且尖端链接张力影响转导通道的开放状态。 Myo1c 的作用是通过调节发束偏转后尖端连杆的静息张力来重置通道打开概率。本研究的目的是了解蛋白激酶 A (PKA) 磷酸化对 Myo1c 调节转导力产生和开放概率的能力的影响。 Myo1c 的 PKA 磷酸化可能会影响 Myo1c 的功能，因为目标位点位于肌球蛋白的拟议柔性区域。 Myo1c 动力学的变化可能会对毛细胞中的转导开放概率产生重大影响。使用生化表征（包括体外运动和 ATP 酶测定以及 Myo1c 的免疫沉淀），将确定 Myo1c 的 PKA 磷酸化的重要性。