Localization of Secretion-Related Proteins in Pancreatic

胰腺分泌相关蛋白的定位

• 批准号: 7319317
• 负责人: Richard D Leapman
• 金额: --
• 依托单位: OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7319317
• 关键词: Localization; Secretion; Related; Proteins; Pancreatic

Molecular mechanisms of regulated exocytosis involving the endocrine-specific protein Resp18 are not yet fully understood. Resp18 was first isolated from a rat pituitary cDNA library in a search for genes that are regulated by dopaminergic drugs. Previously, it has been believed that RESP18 is localized primarily in the endoplasmic reticulum (ER) of neuroendocrine tissues. Since part of RESP18 shares a sequence homology with the luminal region of IA-2, a dense-core vesicle membrane protein involved in vesicle stabilization and biosynthesis, we have tested the hypothesis that RESP18 is implicated in the regulation of dense-core vesicle secretion. Using immuno electron microcopy, we find that RESP18 is mainly expressed in the lumen of DCVs and only to a lesser extent in the ER and Golgi network. Furthermore, double labeling experiments demonstrate that RESP18 is colocalized with insulin in pancreatic beta cell vesicles, as well as with glucagon in pancreatic alpha cell vesicles. The results suggest that RESP18 is a novel luminal protein of regulated secretory vesicles involving the regulated insulin secretion signaling pathway.

涉及内分泌特异性蛋白 Resp18 的受调节胞吐作用的分子机制尚未完全了解。 Resp18 首次从大鼠垂体 cDNA 文库中分离出来，以寻找受多巴胺能药物调节的基因。此前，人们认为RESP18主要位于神经内分泌组织的内质网（ER）中。由于RESP18的一部分与IA-2（一种参与囊泡稳定和生物合成的致密核心囊泡膜蛋白）的管腔区域具有序列同源性，因此我们测试了RESP18参与致密核心囊泡分泌调节的假设。使用免疫电子显微镜，我们发现RESP18主要在DCV管腔中表达，而在内质网和高尔基体网络中表达较少。此外，双标记实验表明，RESP18 与胰腺 β 细胞囊泡中的胰岛素以及胰腺 α 细胞囊泡中的胰高血糖素共定位。结果表明，RESP18是一种新型的调节分泌囊泡管腔蛋白，涉及调节胰岛素分泌信号通路。