Analysis of regulatory mechanisms on autophagy based on the lysosomal distribution.

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15464
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Juntendo University
• Principal Investigator: Sasazawa Yukiko 順天堂大学, 医学(系)研究科(研究院), 特任助教 (20594922)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: オートファジー / リソソーム / 細胞内分布 / メンブレントラフィック

Outline of Final Research Achievements

We recently reported that polyamine metabolism was significantly altered in the serum of Parkinson’s disease patients. To understand its significance, we analyzed the cellular response of polyamine in human neuroblastoma SH-SY5Y cells. We showed that treatment with polyamine changed the lysosomal distribution toward the perinuclear region, and promoted autophagosome-lysosome fusion. Knockdown experiments revealed that one protein X mediated lysosomal distribution change in polyamine-treated cells. Moreover, protein X was phosphorylated by Ca2+/calmodulin-dependent protein kinase in polyamine-treated cells. These data indicated that phosphorylation of protein X is a novel regulatory mechanisms on the lysosomal distribution change.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本成果はリソソーム分布制御、リソソーム-オートファゴソームの融合促進に関わる新しい経路を提示するものである。近年、オートファジーは神経変性疾患だけでなくがんや糖尿病、炎症性腸疾患など、様々な病気に関わることが報告され治療薬開発の標的として注目されているが、実際にオートファジーの経路を特異的に調節する薬剤は少ない。本経路はこれらのオートファジー関連疾患の治療薬開発のための新しいアプローチを示唆している。