Analysis of the mechanism of soluble protein secretion regulated by a small GTPase Rab6

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14692
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Tohoku University
• Principal Investigator: Homma Yuta 東北大学, 生命科学研究科, 助教 (70812642)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 小胞輸送 / 分泌経路 / Rab

Outline of Final Research Achievements

In this study, we investigated the function of a small GTPase Rab6 in the secretory pathway. The total amount of surface transmembrane proteins was not severely affected in Rab6-knockout cells, but their transport efficiency was reduced. Secretion of soluble proteins, including extracellular matrix components, was strongly inhibited in Rab6-knockout cells. These unsecreted proteins were normally transported from the endoplasmic reticulum to the Golgi apparatus, but mistargeted to lysosomes after exit from the Golgi apparatus. These results indicate that Rab6 regulates the post-Golgi transport in the secretory pathway.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

分泌経路は、神経伝達物質やインスリンなどを始め、様々なタンパク質を細胞外（または細胞膜）へと運ぶための主要な輸送経路である。本研究では、低分子量Gタンパク質Rab6がゴルジ体以降の分泌経路を制御することを明らかにしたことで、細胞の基本的な生命現象の一つである分泌経路の全容解明に一歩近づき、また分泌経路に関連する疾患の病態理解などにもつながることが期待される。