Molecular mechanism of synapse differentiation through crosstalk of C1q family molecules and glutamate receptors

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H03562
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Keio University
• Principal Investigator: MATSUDA Keiko 慶應義塾大学, 医学部(信濃町), 講師 (40383765)
• Co-Investigator(Kenkyū-buntansha): 荒井 格 慶應義塾大学, 医学部(信濃町), 助教 (00754631)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: シナプス / グルタミン酸受容体 / カイニン酸受容体

Outline of Final Research Achievements

Splicing specific knockout mouse of neurexin3 exon25b was established, which has been suggested to bind to C1ql family molecules. With a specific antibody both, co-localized synapses were identified. But the interaction of these two molecules was not responsible for either synaptic localization. In splicing specific knockout mouse of neurexin3 exon25b, common abnormality in presynaptic function, defects in synaptic vesicle pooling was observed as C1ql knockout mouse. This indicate that both collaborated and worked on the presynaptic region.In addition, it was discovered that N-terminal region in kainate receptor subunits have ability of presynaptic differentiation. This function was specific in glutamatergic synapse, and the combination with C1ql was not indispensable and there was not the participation of neurexin.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

グルタミン酸受容体の最もアミノ酸末端に存在する細胞外領域（ATD）は全長の3分の1を占めるにもかかわらず、機能は不明なままであった。申請者は、シナプス間隙に突き出たグルタミン酸受容体のATDが、Cblnなど分泌型のシナプス間隙分子と相互作用する足場としての機能を明らかとしてきた。それのみならず、グルタミン酸受容体ATD領域が、直接シナプス前部分子と結合し、特異的なシナプス前部に対しシナプスを挟んでretrogradeに直接働きかけ、シナプス分化を直接司る機能を明らかとした。本研究成果は、これまでイオンチャンネルと考えられてきたグルタミン酸受容体の全く新しい機能を提唱できるものである。