Functional analysis of SNARE proteins in the formation of epithelial cell polarity.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K17847
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including histology/embryology); Cell biology
• Research Institution: Osaka University
• Principal Investigator: Kunii Masataka 大阪大学, 医学系研究科, 助教 (80614768)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 細胞極性 / 細胞内輸送 / SNARE蛋白質 / SNAP23 / 神経発生

Outline of Final Research Achievements

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are essential for the membrane fusion between transport vesicles and target membranes. One of a SNARE proteins, synaptosomal-associated protein of 23 kDa (SNAP23) is known to be involved in membrane fusion between transport vesicles and the plasma membranes; however, the in vivo function of SNAP23 is largely unknown. To elucidate the function of SNAP23, we generated SNAP23 knockout (KO) mice.
The central nervous system (CNS)-specific KO mice showed severe hypoplasia of cerebral cortex and cerebellum, suggesting that SNAP23 is essential for brain development. In the developing KO brain, neural progenitor cells (NPCs) lost their apico-basal polarity by the disruption of apical junctional complexes (AJCs). We found that SNAP23 is important for the apical membrane localization of an AJC protein, N-cadherin. Our results indicate that SNAP23 play a crucial role in the NPC polarization via the formation of AJC.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

これまで、SNAP23の機能に関する研究は主に培養細胞レベルで行われてきた。本研究によってSNAP23が細胞の極性形成を通して組織形成へ関与するという知見は培養細胞レベルの解析では得られないものであり、個体レベルでのSNAP23の機能を解析した本研究は学術的に意義のある成果であると考えられる。また、SNAP23 KOマウスの表現型は大脳皮質の形態異常が生じる滑脳症や二分脊椎、小脳の欠損が生じるダンディー・ウォーカー症候群などの疾患と何らかの関連があることも考えられるため、それらの病態解明や治療法の開発につながる可能性を持っていると考えられる。