The molecular mechanism of synapse organization and modulation via C1q family proteins

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430023
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• 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(Renkei-kenkyūsha): Budisantoso Timotheus 慶應義塾大学, 医学部, 助教 (70724681)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: シナプス / グルタミン酸受容体 / 補体 / 海馬

Outline of Final Research Achievements

Kainate-type ionotropic glutamate receptors (KARs) are highly expressed at synapses between mossy fibers (MFs) and CA3 pyramidal neurons in the hippocampus and important modulators of neural circuit activities. Although diverse KAR roles depend on their subcellular localization, how they are targeted to specific sites is currently unknown. We have demonstarated that the C1q-like proteins C1ql2 and C1ql3, produced by MFs, interact with the amino-terminal domains of postsynaptic GluK2 and GluK4 KAR subunits to determine location and function of KARs. In C1ql2/3-double null mice, CA3 synaptic responses lost the slow, KAR-mediated, components. Furthermore, despite induction of MF sprouting in a temporal lobe epilepsy model, KARs were not recruited to postsynaptic sites in C1ql2/3-double null mice, leading to reduced recurrent circuit activities. C1q-family proteins, broadly expressed, are likely to modulate KAR function throughout the brain.

Free Research Field

神経科学