CAPACITATIVE CA INFLUX BY THE PHOTORECEPTOR CHANNEL TRP

光感受器通道 TRP 的电容性 CA 流入

基本信息

批准号：
6138545
负责人：
H. CRISS HARTZELL
金额：
$ 19.32万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-01-01 至 2001-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6138545
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

项目摘要

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，细胞内储存的 Ca 释放后， Ca 从细胞外间隙流入（“电容性 Ca 进入”）通过商店运营的 Ca 通道 (SOCC)。通过 SOCC 的 Ca 流入量为对于许多细胞活动很重要，包括 T 细胞的激活淋巴细胞通过抗原，从胰腺腺泡分泌胰岛素细胞对促分泌剂的反应和肥大细胞的刺激脱颗粒。尽管 SOCC 很重要，但人们知之甚少关于它们的分子结构或控制机制，但是离子从果蝇光感受器克隆的通道（TRP）可以提供深入了解 SOCC 结构和功能。最近高度保守 TRP 的同系物已在多个物种中被发现，并且似乎 TRP 和这些同系物是 SOCC。该提案的目的是检验 TRP 及其同系物是 SOCC 的假设并使用以下方法研究 TRP 的结构、功能和调节生物物理和分子遗传学方法。具体目标将是研究 TRP 同源物在人体组织中的细胞分布细胞系，以确定膜中 TRP 同系物的拓扑结构，表征 TRP 离子通道同系物的特性在非洲爪蟾卵母细胞和哺乳动物细胞系中，识别辅助细胞通道的亚基，并将秀丽隐杆线虫开发为遗传系统用于研究 TRP 离子通道。这些研究预计将提供关于 Ca 调节机制的宝贵知识细胞。因为细胞内的Ca是信号转导的关键元素几乎在每种细胞类型中都存在级联，我们预计更好的了解这一基本的细胞生物学过程将提供对多种人类疾病的新见解。