Investigation of the Mechanisms Underlying the Differences in Cytoskeletal Assembly at Excitatory and Inhibitory Synapses

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16104
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Gunma University
• Principal Investigator: Ichinose Sotaro 群馬大学, 大学院医学系研究科, 助教 (80775768)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 抑制性シナプス / シナプトジェネシス / 微小管 / シナプスオーガナイザー / キネシン / 神経細胞骨格

Outline of Final Research Achievements

Research on the cytoskeleton that interacts with Teneurin-2, which localizes to both excitatory and inhibitory synapses, suggested that Teneurin-2 may interact with microtubules, although we did not obtain strong data indicating interaction with actin. While both actin and microtubules are present at inhibitory synapses, excitatory synapses are formed on structures called spines, which primarily consist of actin cytoskeleton. Therefore, we shifted our focus to investigate the detailed mechanisms of inhibitory synapse formation mediated by Teneurin-2. It was found that the interaction with microtubules via End binding protein (EB) promotes receptor accumulation.

Free Research Field

神経解剖学・神経細胞生物学

Academic Significance and Societal Importance of the Research Achievements

興奮性シナプスと抑制性シナプスのバランス（E-Iバランス）は自閉症などの発達障害や統合失調症をはじめとする精神疾患との関連が指摘されており、近年盛んに研究されている。今回、われわれは新たなタンパク質相互作用による抑制性シナプス形成の詳細なメカニズムを解明した。今後、このタンパク質相互作用を変化させることのできる新薬を開発することで、シナプス形成を人為的にコントロールできるため、発達障害や精神疾患の治療への応用が期待される。