Relationship between docking and priming steps during insulin granule exocytosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06535
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Gunma University
• Principal Investigator: mizuno kouichi 群馬大学, 生体調節研究所, 助教 (30321821)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 調節性分泌 / インスリン / 開口放出 / 分泌顆粒 / 生細胞観察

Outline of Final Research Achievements

Insulin is secreted from pancreatic β cells by exocytosis. We believe that docking granule, which attaches to the cell membrane, undergo priming and then fuses with plasma membrane in a stimulation-dependent fashion. However, it is still unclear what is happening during priming.This study focused on Munc13, which is known to a priming factor, and aimed to identify Munc13 isoform which involved in insulin secretion and to elucidate its regulatory mechanism of insulin secretion.As a result, it is revealed that ubiquitous form of Munc13b is a priming factor controlling the insulin granule exocytosis. It is also clarified that priming occurs just before exocytosis, based on the observation that Munc13b accumulates onto docking granules just before exocytosis.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究によりインスリン顆粒の開口放出を制御するプライミング因子が遍在型Munc13bであること、またプライミングが起きるのは、開口放出直前であることを明らかにした。この知見は、神経細胞とは異なる内分泌細胞特有の開口放出制御機構の解明に貢献するだけでなく、Munc13bを標的としたドッキング顆粒からのインスリン分泌を促進する新たな作用機序を持つ糖尿病治療薬の開発に繋がる可能性がある。