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：（根据研究者的摘要改编）电离钙（Ca2+） 充当听力必不可少的细胞内信号。管理这个 信号，CA2+通道和泵是必要的。最近的研究表明 质膜Ca2+泵（PMCA）高度集中在尖端 立体膜的毛细细胞中是唯一的Ca2+挤出系统。昏死 缺乏PMCA的同工型2的小鼠聋哑，表现出严重的平衡缺陷。 菌株的老鼠名为“聋哑人”和“蠕动”，它们具有类似的赤字， 最近发现在同一PMCA2中突变是纯合的 基因。根据这些发现，该提案将探索功能 主要PMCA同工型的特性和特定相互作用蛋白 内耳。具体目的是（1）确定哪些PMCA型和 替代剪接变体以啮齿动物耳蜗和前庭头发表示 细胞； （2）确定主要“聋人”的功能性能 和“蠕动” PMCA突变体和其他单一氨基酸突变体； （3） 识别和表征与主要PMCA相互作用的蛋白质 毛细胞的Ioform，可能是其独特定位的原因 到立体尾tip。这些实验将建立一个新的领域 调查质膜Ca2+泵作为控制器的作用 内耳中局部Ca2+调节的法规，应导致更好 对其对听力过程的贡献表示赞赏。