Images of カイニン酸型グルタミン酸受容体
脳の働きを分子から考える その3 〜孤児からオーガナイザーへ デルタ型グルタミン酸受容体の話(2020年7月20日公開)図1:遺伝子クローニングが行われていた当時、グルタミン酸受容体がNMDA型やAMPA/カイニン酸型というイオンチャネルに分類されることは予想されていたが、デルタ型についてはリガンドも機能も不明であり、長い間"孤児受容体"と呼ばれていた。図2:GluD2サブユニットはニューレキシン( Neurexin )とCbln1と三者複合体を構成し、平行線維-プルキンエ細胞間のシナプス結合を形成させるシナプスオーガナイザーとして機能する。一方、 GluD2サブユニットの細胞外のリガンド結合領域にはD-セリンが結合し、細胞内C末端領域にはチロシン脱リン酸化酵素PTPMEGが結合して、長期抑圧に重要な役割を果たしている。図3:(A)組織学的解析と(B)生化学的解析より明らかとなったポストシナプスでのデルタ型グルタミン酸受容体の局在様式。同一のシナプスにGluD1とGluD2の両方のサブユニットが存在し、免疫沈降法によりGluD1サブユニット抗体でGluD2サブユニットが共沈することが示された。(C)うつ様行動の指標となる強制水泳テストにおいてGluD1欠損マウスが示す無動時間の増加。この異常は抗うつ薬イミプラミンとフルオキセチンにより回復することが示された。(文献33, 34より改変)Hollmann M, Heinemann S: Cloned glutamate receptors. Annual review of neuroscience 1994, 17:31-108.Yamazaki M, Araki K, Shibata A, Mishina M: Molecular cloning of a cDNA encoding a novel member of the mouse glutamate receptor channel family. 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