ROLE OF THE PLASMA MEMBRANE CALCIUM PUMP IN HEARING

等离子膜钙泵在听力中的作用

• 批准号: 6379511
• 负责人: JOHN T PENNISTON
• 金额: $ 25.24万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6379511
• 关键词: calcium flux; calcium transporting ATPase; ear hair cell; hearing; immunocytochemistry; in situ hybridization; isozymes; laboratory mouse; laboratory rat; mutant; polymerase chain reaction; protein localization; yeast two hybrid system

DESCRIPTION: (Adapted from the Investigator's Abstract) Ionized calcium (Ca2+) acts as an intracellular signal which is essential to hearing. To manage this signal, Ca2+ channels and pumps are necessary. Recent studies have shown that the plasma membrane Ca2+ pump (PMCA), which is highly concentrated in the tips of the stereocilia, is the sole Ca2+ extrusion system in hair cells. Knockout mice lacking isoform 2 of the PMCA are deaf and show severe balance deficits. Mice of strains named "deafwaddler" and "wriggle," which have similar deficits, have recently been found to be homozygous for a mutation in the same PMCA2 gene. Based on these findings, the proposal will explore the functional properties and specific interacting proteins of the major PMCA isoform(s) of the inner ear. The specific aims are (1) to determine which PMCA ioforms and alternative splice variants are expressed in rodent cochlea and vestibular hair cells; (2) to determine the functional properties of the major "deafwaddler" and "wriggle" PMCA mutants and of additional single amino acid mutants; and (3) to identify and characterize the proteins that interact with the major PMCA ioform of the hair cells, which may be responsible for its unique localization to the stereocilia tips. These experiments will establish a new area of investigation into the role of the plasma membrane Ca2+ pump as the controller of local Ca2+ regulation in the inner ear and should lead to a better appreciation of its contribution to the process of hearing.

描述：（改编自研究者摘要）离子钙（Ca 2+） 作为一种细胞内信号，对听觉至关重要。管理此 信号、Ca 2+通道和泵是必需的。最近的研究表明 质膜钙泵（PMCA），其高度集中在尖端 是毛细胞中唯一的Ca ~（2+）外排系统。敲除 缺乏PMCA同种型2的小鼠是聋的，并表现出严重的平衡缺陷。 被命名为“蹒跚”和“蠕动”的小鼠品系具有相似的缺陷， 最近发现在同一PMCA 2中的突变是纯合的 基因根据这些调查结果，本提案将探讨 主要PMCA亚型的特性和特异性相互作用蛋白 内耳具体目标是（1）确定哪些PMCA形式， 选择性剪接变体在啮齿动物耳蜗和前庭毛中表达 细胞;（2）确定主要的“蹒跚学步者”的功能特性 和“蠕动”PMCA突变体和另外的单氨基酸突变体;和（3） 鉴定和表征与主要PMCA相互作用的蛋白质 毛细胞的ioform，这可能是负责其独特的定位 到静纤毛尖端这些实验将建立一个新的领域 质膜Ca ~（2+）泵作为控制器的研究 局部Ca 2+调节内耳，并应导致更好的 感谢他们对听证会的贡献。