Mechanism of how Stx17 changes its functions in response to nutrition status

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02480
• 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: Tokyo Dental College (2023); Tokyo University of Pharmacy and Life Science (2021-2022)
• Principal Investigator: TAGAYA MITSUO 東京歯科大学, 歯学部, 客員教授 (30179569)
• Co-Investigator(Kenkyū-buntansha): 井上 弘樹 東京薬科大学, 生命科学部, 講師 (10294448) ; 若菜 裕一 東京薬科大学, 生命科学部, 助教 (90635187)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: syntaxin 17 / 小胞体 / ミトコンドリア / オートファジー / 脂肪滴 / リン酸化

Outline of Final Research Achievements

Syntaxin 17 (Stx17) is localized in the MAM (mitochondria-associated membrane) and mitochondria, and exhibits various functions in response to nutrient situation by binding to different partners. In this study, we obtained the following observations. (1) The localization and function of Stx17 depend on the structure of the C-terminal tail that largely varies in organisms. Lys254, the C-terminal long hydrophobic region (CHD), and its precedent positively charged residues also contribute to the determination of Stx17 localization. (2) In fed state, Stx17 at Ser134 is phosphorylated and its dephosphorylation upon starvation causes Stx17 to function in formation of autophagosomes and lipid droplets. (3) As seen in energy excess conditions, ACSL3 is activated by Stx17 to form lipid droplets upon starvation. ACSL3 also plays a role in autophagosome formation. (4) CPT1A functions as a reservoir for Stx17 and ACSL3.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

小胞体とミトコンドリアの接触領域は脂質合成に留まらず、ミトコンドリアのダイナミクス、オートファジー、インフラソームの形成などを司り、Stx17はこれらの生命現象に関与する。本研究によって、Stx17が多様な機能を発揮することができる分子的基盤の一端が明らかとなった。小胞体とミトコンドリアの接触領域は、パーキンソン病などの神経変性疾患や糖尿病の発症とも密接に関係しており、本研究はこれらの病気の発症機序の解明にも貢献すると考えられる。