RABPHILIN3A AND EXOCYTOSIS AND CHROMAFFIN CELLS

RABPHILIN3A 与胞吐作用和嗜铬细胞

• 批准号: 2017024
• 负责人: RONALD W HOLZ
• 金额: $ 23.71万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-14 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2017024
• 关键词: antisense nucleic acid; chemical kinetics; chromaffin cells; cytoskeleton; exocytosis; mutant; protein structure function; proteins; secretion; single cell analysis; somatotropin; tissue /cell culture; transfection

DESCRIPTION: Exocytotic release of hormones and neurotransmitters is central to intercellular communication and synaptic transmission and is fundamental to the normal function of the endocrine, cardiovascular and nervous systems. The long-term goal of the application is to understand the biochemical and physiological mechanisms underlying regulated exocytosis. Specifically, this application will elucidate the role of rabphilin3a in the pathway. Rab GTPases are involved in vesicular trafficking in the secretory and endocytotic pathways. Rabphilin3a was identified in brain as a possible effector for rab3a. The investigators recently found that rabphilin3a is expressed with rab3a in adrenal chromaffin cells and enhances calcium dependent secretion. The focus of this proposal is to investigate the mechanisms by which rabphilin3a functions in regulated exocytosis. The proposal will: 1) elucidate the mechanism by which rabphilin3a enhances exocytosis in bovine adrenal chromaffin cells using both biochemical and electrophysiological measures of secretion. 2) Determine the relationship between subcellular localization of rabphilin3a and mutants and function in secretion. 3) Investigate possible new members of the rabphilin3a pathway including adducin. A variety of techniques will be used to study rabphilin3a function in chromaffin cells including transient-expression approach for biochemical studies of secretion and electrophysiological/microamperometric techniques from single cell studies.

描述：激素和神经递质的胞吐释放， 是细胞间通讯和突触传递的中心， 对内分泌、心血管和 神经系统 应用程序的长期目标是了解 调节胞吐作用的生化和生理机制。 具体地，本申请将阐明rabphilin 3a在细胞凋亡中的作用。 通路 Rab GTP酶参与分泌性细胞中的囊泡运输。 和内吞途径。 Rabphilin 3a在脑中被鉴定为可能的 rab 3a的效应器。 研究人员最近发现，rabphilin 3a是 rab 3a在肾上腺嗜铬细胞中表达，并增强钙离子浓度。 依赖性分泌 本提案的重点是调查 rabphilin 3a在调节胞吐中起作用的机制。 的 该提案将：1）阐明rabphilin 3a增强 牛肾上腺嗜铬细胞的胞吐作用， 分泌的电生理测量。 2)确定关系 rabphilin 3a和突变体的亚细胞定位和功能之间的关系， 分泌物 3)研究rabphilin 3a途径的可能新成员 包括内收蛋白。 将使用各种技术来研究 rabphilin 3a在嗜铬细胞中的功能，包括瞬时表达 分泌物的生物化学研究方法， 电生理学/微安培技术从单细胞研究。