Biological roles of novel proteolytic mechanism GOMED

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H01533
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: shimizu shigeomi 東京医科歯科大学, 難治疾患研究所, 教授 (70271020)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: GOMED / 新規オートファジー / ゴルジ体 / Atg5 / Ulk1

Outline of Final Research Achievements

The Golgi membrane-associated degradation pathway (GOMED) is a mechanism that degrades undelivered plasma membrane proteins and secretory proteins upon Golgi stress. GOMED is a unique and novel Golgi function involving dramatic morphological changes in the Golgi.
(1) We here identified five GOMED-associated molecules, and identified their signaling pathways. (2) We also clarified the role ofGOMED in neurons and pancreatic beta cells. (3) We developed the methods to detect GOMED using Ulk1 phosphorylation and small fluorescence compound. (4) We identified cytosolic accumulation of undelivered Golgi molecules, and which induces cell injury.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

GOMED機能は、ホルモンやサイトカインなどの細胞外分泌や細胞膜レセプターの発現量を調節する機能として、我々が発見した新たな細胞機能です。本研究では、GOMED機構がどのようにして実行されるか、どの細胞で実行されるか、この機構が働かないと如何なる障害が起こるかを研究しました。その結果、神経細胞の維持やホルモン分泌制御に決定的な役割を果たしてることを発見しました。また、この機構の検出方法も明らかにし、今後病気への応用が期待されます。