Research on the role of Sez6 splicing variants in neural network formation and plasticity

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17064
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Kochi University
• Principal Investigator: Hidaka Chiharu 高知大学, 教育研究部医療学系基礎医学部門, 助教 (10783673)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: Sez6 / スプライスバリアント / 膜タンパク質

Outline of Final Research Achievements

In this study, we investigated whether seizure-related gene 6 (Sez6) expression is temporally and spatially regulated by alternative splicing processes. Sez6, a transmembrane protein specifically localized on neuronal dendrites, is responsible for dendritic branching and synapse formation. However, its exact role in neural network formation remains unclear. Our study revealed that Sez6 splicing patterns were modulated in a brain area-specific manner. In particular, the striatum showed a characteristic splicing pattern of recessive isoforms. Moreover, neuronal activation by convulsant drug stimulation increased the levels of recessive isoforms like that of the dominant isoform in cultured neurons. Additionally, we produced expression vectors of each Sez6 splicing isoform and confirmed their expression. Future work should investigate whether each of the Sez6 isoforms affects neural network formation and maintenance when overexpressed in neurons.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

認知機能をはじめとした高度脳機能の機能発現には神経細胞間で形成される神経回路網が極めて重要である。したがってこの認知機能の機能発現機構の形成・維持の機序を詳細に明らかにしていくことは、超高齢化社会に向けて社会全体が大きく舵を切って行くことがほぼ確実視されている今日の日本においては特に重要なテーマである。本研究課題が神経回路形成の機序の本質的な理解の足掛かりとなることで、将来的には高次脳機能の発現の仕組みを理解する新たな視座をの提供を目指していきたい。