Study on the mechanism of CAPS-dependent secretory vesicle exocytosis and its deficits in the nervous system and behavior

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03563
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo University of Science
• Principal Investigator: Furuichi Teiichi 東京理科大学, 理工学部応用生物科学科, 教授 (50219094)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: CAPS / シナプス小胞 / 有芯小胞 / 開口放出 / 学習記憶行動 / 社会行動 / プロオピオメラノコルチン / オキシトシン

Outline of Final Research Achievements

Classical and peptidic neurotransmitters are taken up by small synaptic vesicles (SVs) and large dense-core vesicles (DCVs) that are produced in different ways, and then released by a similar exocytosis phenomenon. The purpose of this study was to clarify the functional role of CAPS proteins involved in both exocytosis and their significance in physiology and behavior. It was suggested that CAPS1 is involved in exocytosis of glutamatergic SVs in the hippocampus, has an important role in synaptic transmission and plasticity, and is essential for learning memory. It was suggested that CAPS2 is involved in exocytosis of proopiomelanocortinergic and oxytocinergic DCVs, and plays an important role in the control of feeding and the expression of social behavior, respectively.

Free Research Field

神経化学

Academic Significance and Societal Importance of the Research Achievements

CAPS1は，興奮性グルタミン酸シナプス小胞の開口放出機構に関与し，海馬シナプス伝達，シナプス可塑性の回路機能から，学習記憶行動まで重要な役割をもつ。CAPS2は，神経ペプチドを含む有芯小胞の開口放出機構に関与し，CAPS2依存的なプロオピオメラノコルチン分泌は摂食行動に，CAPS2依存的なオキシトシン分泌は社会行動に，それぞれ関連することが示された。これらの研究成果から，中枢神経系の古典的とペプチド性の神経伝達物質をそれぞれ含有するシナプス小胞と有芯小胞の開口放出機構が，CAPSという共通のタンパク質によって制御されており，この欠損が多様な神経機能異常を引き起こすことが解明された。