Images of NMDA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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The Journal of neuroscience : the official journal of the Society for Neuroscience 2014, 34(22):7412-7424.Kashiwabuchi N, Ikeda K, Araki K, Hirano T, Shibuki K, Takayama C, Inoue Y, Kutsuwada T, Yagi T, Kang Y et al: Impairment of motor coordination, Purkinje cell synapse formation, and cerebellar long-term depression in GluR delta 2 mutant mice. Cell 1995, 81(2):245-252.Kohda K, Kakegawa W, Matsuda S, Yamamoto T, Hirano H, Yuzaki M: The δ2 glutamate receptor gates long-term depression by coordinating interactions between two AMPA receptor phosphorylation sites. Proceedings of the National Academy of Sciences 2013, 110(10):E948-E957.Takeuchi T, Ohtsuki G, Yoshida T, Fukaya M, Wainai T, Yamashita M, Yamazaki Y, Mori H, Sakimura K, Kawamoto S et al: Enhancement of both long-term depression induction and optokinetic response adaptation in mice lacking delphilin. 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The Journal of neuroscience : the official journal of the Society for Neuroscience 2010, 30(45):15196-15209.Yamasaki M, Miyazaki T, Azechi H, Abe M, Natsume R, Hagiwara T, Aiba A, Mishina M, Sakimura K, Watanabe M: Glutamate receptor delta2 is essential for input pathway-dependent regulation of synaptic AMPAR contents in cerebellar Purkinje cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 2011, 31(9):3362-3374.Hirai H, Pang Z, Bao D, Miyazaki T, Li L, Miura E, Parris J, Rong Y, Watanabe M, Yuzaki M et al: Cbln1 is essential for synaptic integrity and plasticity in the cerebellum. Nature neuroscience 2005, 8(11):1534-1541.Matsuda K, Miura E, Miyazaki T, Kakegawa W, Emi K, Narumi S, Fukazawa Y, Ito-Ishida A, Kondo T, Shigemoto R et al: Cbln1 is a ligand for an orphan glutamate receptor delta2, a bidirectional synapse organizer. 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NMDA-Rezeptor
NMDA receptor
Receptor NMDA
NMDA-reseptori
Récepteur NMDA
NMDA-receptor
NMDA-рецептор
NMDA reseptörü
