Rapid regulation of sialidase activity in response to neural activity and sialic acid removal during memory processing

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08277
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: Minami Akira 静岡県立大学, 薬学部, 講師 (80438192)
• Research Collaborator: Suzuki Takashi ; Ikeda Kiyoshi ; Kanazawa Hiroaki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: シアリダーゼ / 神経 / 海馬 / 記憶 / 糖鎖 / 蛍光プローブ / シアル酸 / in vivo

Outline of Final Research Achievements

We previously found that sialidase, which removes an acidic sugar molecule from the end of the sugar chain, rapidly changes enzyme activity in response to neural excitation on the cell surface and is essential for memory formation. If the sugar chain structure is regulated on the cell surface, it is possible to change the sugar chain structure instantaneously. In this study, based on the working hypothesis that “a rapid change in sugar chain structure in response to neural excitation controls neural circuit formation during memory formation”, the function of sialidase in memory was investigated by using a novel analysis tools for glycans. The present study revealed that sialic acid detaches during memory formation, and that this detachment is one of the negative feedback mechanisms for glutamate release and is related to the long-term potentiation that is the basic principle of memory.

Free Research Field

神経糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

神経における糖鎖の機能解析は、タンパク質の機能解析などと比較して遅れている。その原因として、糖鎖機能の解析ツールが限られていることが挙げられる。記憶などの極めて短時間で変化する現象において糖鎖の役割を理解するためには、新たな糖鎖機能の解析ツールが必要である。本研究では研究代表者らが開発した新たな糖鎖機能分析ツールを利用することにより、神経興奮に伴って糖鎖構造が極めて短いタイムスケール（単位：秒や分）で厳密に制御されていることが明らかになった。この研究成果を基盤として、現在全く新しい視点から疾患や生理機能の機能解明に取り組んでいる