Mechanisms of axonal development by the glycolipid metabolism at organelle contact sites

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15198
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: The University of Tokyo
• Principal Investigator: Tsuboi Masafumi 東京大学, 大学院工学系研究科(工学部), 助教 (20847123)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 小胞体-リソソーム接触 / ニューロン / 糖脂質

Outline of Final Research Achievements

Neurons exhibit a highly polarized structure, and the development and maintenance of this unique morphology are believed to rely on the regulation of glycolipids. The glycolipid synthesis pathway has been demonstrated to be crucial for axonal development. However, the significance of the salvage pathway, in which glycolipids are degraded into ceramides in lysosomes and then recycled to the endoplasmic reticulum (ER), is still not fully understood. In this study, we examined whether PDZD8, which is located at the ER-lysosome contact sites, contributes to the regulation of the salvage pathway and is necessary for axonal development., We found that PDZD8 is required for the formation of axonal branches in cortical callosal neurons through an shRNA-based knockdown study, and this requirement may not be mediated by the glycolipid metabolism pathway.

Free Research Field

神経発生生物学

Academic Significance and Societal Importance of the Research Achievements

オルガネラは細胞内の適切なコンパートメントに局在し、細胞全体の恒常性維持のみならず細胞の局所的な機能発揮に必須の役割を果たす。近年オルガネラは単独で働くのではなく、接触面において脂質やイオン交換など重要な生体反応をしていることが明らかになっているが、その生理的役割は未解明な点が多い。本研究から、両接触場に局在するPDZD8が軸索分岐形成に寄与する可能性を示し、オルガネラ接触場の新たな機能を明らかにした。