Molecular Mechanisms for the formation of periodic cytoskeletal structures in axons

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K07118
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Osaka University
• Principal Investigator: YOSHIMURA Takeshi 大阪大学, 連合小児発達学研究科, 講師 (60402567)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 神経細胞 / 軸索 / 細胞骨格 / Spectrin / リン酸化

Outline of Final Research Achievements

Axons have a specific cytoskeletal structure lining the cytoplasmic face of the axolemma. Super-resolution microscopy has revealed a remarkable periodic lattice in axons. αII-spectrin is the only α spectrin detected in the nervous system, and forms the periodic lattice in axons. While αII-spectrin intracellular localization is fairly well understood, the molecular mechanism by which αII-spectrin was regulated remains unclear. In this study, we report that Cdk5 phosphorylates αII-spectrin. We identified the phosphorylation site of αII-spectrin by Cdk5, and made anti-phospho-specific αII-spectrin antibody. The phosphorylated αII-spectrin was localized in the axon initial segment. Inhibition of Cdk5 impaired axon initial segment formation and neuronal polarity. These results suggest that Cdk5 regulates the axonal periodic cytoskeleton through the phosphorylation of αII-spectrin.

Free Research Field

分子神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、神経細胞においてCdk5はαII-spectrinのリン酸化を介して軸索特異的な細胞骨格構造の形成に重要な役割を果たすことが明らかとなった。本研究により軸索に特異的な細胞骨格の形成機構が分かることで、情報出力を担う軸索の基盤の理解が深まると考えられる。ウエスト症候群は既知の小児難治てんかんの中では最も多い、精神運動発達の退行を伴う指定難病である。この疾患に関わるαII-spectrinの制御機構の解明はその病因解明の糸口になると期待される。