Analysis of a novel sorting mechanism of soluble secretory proteins in the Golgi

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03220
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: Tohoku University
• Principal Investigator: Fukuda Mitsunori 東北大学, 生命科学研究科, 教授 (50311361)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 低分子量Gタンパク質Rab / 分泌経路 / 上皮細胞 / Rab panel / スクリーニング / ノックアウト細胞 / 可溶性蛋白質 / 膜輸送

Outline of Final Research Achievements

In the secretory pathway, soluble secretory proteins and membrane proteins are packed into small vesicles, which are transported from the endoplasmic reticulum (ER), to the Golgi apparatus, and eventually to the plasma membrane. In general, soluble secretory proteins and membrane proteins are packed into the “same transport vesicles” in the ER, and a similar mechanism is thought to be used when both proteins are sorted into transport vesicles even in the Golgi, although their sorting and transport mechanisms are poorly understood. In this study, we found that Rab6 plays an important role in secretion of soluble secretory proteins. In Rab6-knockout cells, secretion of soluble secretory proteins to the culture medium was generally impaired, whereas transport of transmembrane proteins to the plasma membrane was only mildly affected. Based on our findings, we suggest that soluble secretory proteins and transmembrane proteins are mostly segregated into different post-Golgi vesicles.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、可溶性蛋白質と膜蛋白質は必ずしも同じ輸送小胞に選別されるのではなく、少なくともRab6非存在下では、両者が異なる小胞に選別されている可能性が極めて高いことが明らかになった。今後、Rab6に依存しない膜蛋白質の輸送の詳細な仕組みが明らかになれば、教科書の記載変更にもつながるものと期待される。
また、我々の体を構成する細胞は、コラーゲンなど生理学的に重要な様々な可溶性蛋白質を細胞外へと放出している。本研究により明らかになったRab6とその結合分子を介する分泌の詳細な分子基盤が明らかになれば、将来的には、薬剤スクリーニング等による人為的な分泌制御にも発展する可能性を秘めている。