Molecular Mechanisms for axon initial segment plasticity in neurons

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06855
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Osaka University
• Principal Investigator: Yoshimura Takeshi 大阪大学, 大学院連合小児発達学研究科, 講師 (60402567)
• Co-Investigator(Kenkyū-buntansha): 臼井 紀好 大阪大学, 大学院医学系研究科, 准教授 (00784076)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 神経細胞 / 軸索起始部 / 細胞骨格 / Ankyrin-G / リン酸化

Outline of Final Research Achievements

The axon initial segment (AIS) is plastic and may change in response to activity and disease. The molecular mechanism by which the AIS forms remains unclear. In this study, we report that Cdk5 phosphorylates ankyrin-G, a master organizer of AIS. We identified the phosphorylation site of ankyrin-G by Cdk5. We observed abnormalities in AIS length in rodent models of attention-deficit hyperactivity disorder and autism spectrum disorder. These results suggest that Cdk5 regulates the AIS formation through the phosphorylation of ankyrin-G. Abnormal neuronal output due to abnormalities in the AIS may contribute to the pathophysiology of neurodevelopmental disorders such as attention-deficit hyperactivity disorder and autism spectrum disorder.

Free Research Field

分子神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究結果から、Cdk5はankyrin-Gのリン酸化を介して軸索起始部に特異的な細胞骨格構造の形成に重要な役割を果たしており、注意欠如・多動症や自閉スペクトラム症様モデル動物においてそのリン酸化制御が破綻していると考えられる。Ankyrin-G (ANK3)のヒト遺伝子変異により注意欠如・多動症や自閉スペクトラム症などが引き起こされることが報告されており、本研究は注意欠如・多動症や自閉スペクトラム症の病態解明の手がかりになることが期待される。