カイニン酸型グルタミン酸受容体(KAR)が, 海馬歯状回顆粒細胞の軸索(苔状線維 : MF)とCA3細胞間のシナプス後部に局在化する機構は不明であったが, シナプス前部MFから放出されるC1ql2およびC1ql3が, シナプスを越えてシナプス後部細胞に発現するKARと直接結合することによって, 局在化を制御する機構を明らかとした。C1ql2およびC1ql3を二重欠損させたマウスではMF-CA3シナプス後部でKARが消失し, てんかん誘発モデルでの異常分枝シナプスにもKARが集積しなかった。このようにC1ql2/3はシナプス後部へのKARの組み込みと機能を制御することで適切な神経ネットワーク活動を作り上げる。
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.
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