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ROLE OF THE PLASMA MEMBRANE CALCIUM PUMP IN HEARING

等离子膜钙泵在听力中的作用

基本信息

批准号：
6523489
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
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-09-01 至 2004-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6523489
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

项目摘要

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《调查者摘要》)离子钙(钙离子) 起到了细胞内信号的作用，这对听力是必不可少的。要管理好这一点信号、钙离子通道和泵是必要的。最近的研究表明，质膜钙泵(PMCA)，它高度集中在顶端在立体纤毛中，是毛细胞中唯一的钙排泄系统。淘汰赛缺乏PMCA亚型2的小鼠是聋人，表现出严重的平衡缺陷。名为“deafwaddler”和“wrigger”的品系的小鼠有类似的缺陷，最近发现同一PMCA2中的突变是纯合的吉恩。基于这些发现，该提案将探索功能猪瘟病毒主要亚型(S)的性质和特异性相互作用蛋白内耳。具体目标是(1)确定哪些PMCA碘形成和选择性剪接变异体在啮齿动物的耳蜗和前庭毛发中表达细胞；(2)确定主要的“deafwaddler”的功能特性和“蠕动”PMCA突变体和额外的单一氨基酸突变体；以及(3) 鉴定和鉴定与主要PMCA相互作用的蛋白质毛细胞的Ioform，这可能是其独特定位的原因到立体纤毛的尖端。这些实验将建立一个新的领域质膜钙泵作为调节器作用的研究在内耳的局部钙离子调节，应该会导致更好的赞赏其对听证进程的贡献。