CAPACITATIVE CA INFLUX BY THE PHOTORECEPTOR CHANNEL TRP

光感受器通道 TRP 的电容性 CA 流入

• 批准号: 2634829
• 负责人: H. CRISS HARTZELL
• 金额: $ 18.3万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2634829
• 关键词: Caenorhabditis elegans; Drosophilidae; Xenopus oocyte; animal genetic material tag; calcium channel; calcium flux; genetically modified animals; glycosylation; human tissue; molecular cloning; nucleic acid sequence; protein structure function; suppressor mutations; visual photoreceptor

In many cells, release of Ca from intracellular stores is followed by Ca influx from the extracellular space ("capacitative Ca entry") through store-operated Ca channels (SOCCs). Ca influx through SOCCs is important for many cellular activities including activation of T lymphocytes by antigen, secretion of insulin from pancreatic acinar cells in response to secretagogues, and stimulation of mast cell degranulation. Despite the importance of SOCCs, very little is known about their molecular structure or control mechanisms, but an ion channel (TRP) cloned from Drosophila photoreceptors may provide insights into SOCC structure and function. Recently, highly conserved homologs of TRP have been identified in several species and it appears that TRP and these homologs are SOCCs. The purpose of this proposal is to test the hypothesis that TRP and its homologs are SOCCs and to investigate the structure, function, and regulation of TRPs using biophysical and molecular genetic approaches. Specific aims will be to study the cellular distribution of TRP homologs in human tissues and cell lines, to determine the topology of TRP homologs in the membrane, to characterize the properties of TRP ion channel homologs expressed in Xenopus oocytes and mammalian cell lines, to identify accessory subunits of the channel, and to develop C. elegans as a genetic system for studying TRP ion channels. These studies are expected to provide valuable knowledge about the mechanisms by which Ca is regulated in cells. Because intracellular Ca is a key element in signal transduction cascades in virtually every cell type, we anticipate that a better understanding of this fundamental cell biological process will provide new insights into a variety of human diseases.

在许多细胞中，从细胞内存储中释放Ca之后是 CA从细胞外空间涌入（“电容性CA进入”） 通过商店经营的CA渠道（SOCC）。通过SOCC的CA涌入是 对于许多细胞活动，包括激活T 通过抗原，胰岛细胞分泌胰岛素的淋巴细胞 细胞响应促分泌物和刺激肥大细胞 脱粒。尽管SOCC很重要，但知之甚少 关于它们的分子结构或控制机制，但一个离子 从果蝇光感受器克隆的通道（TRP）可能会提供 深入了解SOCC结构和功能。最近，高度保守 TRP的同源物已在几种物种中鉴定出来，似乎 TRP和这些同源物是SOCC。该提议的目的是 检验TRP及其同源物是SOCC的假设 使用使用TRP的结构，功能和调节 生物物理和分子遗传学方法。具体目标是 研究人体组织中TRP同源物的细胞分布和 细胞系，确定膜中TRP同源物的拓扑， 表征表达的TRP离子通道同源物的属性 在Xenopus卵母细胞和哺乳动物细胞系中，以识别附件 通道的亚基，并将秀丽隐杆线虫作为遗传系统发展 用于研究TRP离子通道。这些研究有望提供 关于CA的机制的宝贵知识 细胞。因为细胞内CA是信号转导的关键要素 几乎每种单元格中的级联 了解这种基本细胞生物过程将提供 对各种人类疾病的新见解。