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2021 Fiscal Year Final Research Report

Regulation of synaptic plasticity by heparan sulfate 6-O sulfatase (Sulf)

Research Project

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Project/Area Number 18K06145
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43030:Functional biochemistry-related
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

KAMIMURA Keisuke  公益財団法人東京都医学総合研究所, 脳・神経科学研究分野, 主席研究員 (30529524)

Project Period (FY) 2018-04-01 – 2022-03-31
Keywordsへパラン硫酸 / プロテオグリカン / ヘパラン硫酸6-O脱硫酸化酵素 / シナプス可塑性 / 自閉症
Outline of Final Research Achievements

To investigate the role of fine structures of the heparan sulfate (HS) chains in synaptic plasticity, we focused on the neuromuscular junction of Drosophila, a model of glutamatergic synapses. In Drosophila, starvation is known to increase the number of synaptic terminals at the neuromuscular junction. However, it was found that the number of synaptic boutons did not increase in starved animals lacking the 6-O sulfatase (Sulf1) that desulfates the 6-O position of the HS chain. In addition, the starvation dependent increase of glutamate receptor GluRIIA was inhibited in Sulf1 mutants. These results suggest that fine structures of the HS chains regulate synaptic plasticity.

Free Research Field

糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

近年、ニューレキシンなどのHSPGに加え、いくつかのHS修飾酵素の変異が自閉症及び統合失調症の発症に関与することが報告されている。しかしながら、HS鎖の修飾異常がどのように影響することで疾患の発症に関与するのかはわかっていない。したがって、本研究においてHS修飾酵素によるシナプス可塑性調節機構を明らかにしたことは神経・精神疾患治癒を目標とした医学的研究においても極めて重要である。

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Published: 2023-01-30  

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