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. Biochemical and biophysical research communications 1992, 183(2):886-892.Araki K, Meguro H, Kushiya E, Takayama C, Inoue Y, Mishina M: Selective Expression of the Glutamate Receptor Channel δ2 Subunit in Cerebellar Purkinje Cells. Biochemical and biophysical research communications 1993, 197(3):1267-1276.Lomeli H, Sprengel R, Laurie DJ, Köhr G, Herb A, Seeburg PH, Wisden W: The rat delta-1 and delta-2 subunits extend the excitatory amino acid receptor family. FEBS letters 1993, 315(3):318-322.Konno K, Matsuda K, Nakamoto C, Uchigashima M, Miyazaki T, Yamasaki M, Sakimura K, Yuzaki M, Watanabe M: Enriched expression of GluD1 in higher brain regions and its involvement in parallel fiber-interneuron synapse formation in the cerebellum. 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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Neuroscience research 2001, 41(2):193-200.Ady V, Perroy J, Tricoire L, Piochon C, Dadak S, Chen X, Dusart I, Fagni L, Lambolez B, Levenes C: Type 1 metabotropic glutamate receptors (mGlu1) trigger the gating of GluD2 delta glutamate receptors. EMBO reports 2014, 15(1):103-109.Takeuchi T, Miyazaki T, Watanabe M, Mori H, Sakimura K, Mishina M: Control of synaptic connection by glutamate receptor delta2 in the adult cerebellum. The Journal of neuroscience : the official journal of the Society for Neuroscience 2005, 25(8):2146-2156.Miyazaki T, Yamasaki M, Takeuchi T, Sakimura K, Mishina M, Watanabe M: Ablation of glutamate receptor GluRδ2 in adult Purkinje cells causes multiple innervation of climbing fibers by inducing aberrant invasion to parallel fiber innervation territory. 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. Science (New York, NY) 2010, 328(5976):363-368.Uemura T, Lee SJ, Yasumura M, Takeuchi T, Yoshida T, Ra M, Taguchi R, Sakimura K, Mishina M: Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum. Cell 2010, 141(6):1068-1079.Matsuda K, Yuzaki M: Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions. The European journal of neuroscience 2011, 33(8):1447-1461.Kakegawa W, Mitakidis N, Miura E, Abe M, Matsuda K, Takeo YH, Kohda K, Motohashi J, Takahashi A, Nagao S et al: Anterograde C1ql1 signaling is required in order to determine and maintain a single-winner climbing fiber in the mouse cerebellum. Neuron 2015, 85(2):316-329.Matsuda K, Budisantoso T, Mitakidis N, Sugaya Y, Miura E, Kakegawa W, Yamasaki M, Konno K, Uchigashima M, Abe M et al: Transsynaptic Modulation of Kainate Receptor Functions by C1q-like Proteins. 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The Journal of comparative neurology 2020, 528(6):1003-1027.Nakamoto C, Kawamura M, Nakatsukasa E, Natsume R, Takao K, Watanabe M, Abe M, Takeuchi T, Sakimura K: GluD1 knockout mice with a pure C57BL/6N background show impaired fear memory, social interaction, and enhanced depressive-like behavior. PloS one 2020, 15(2):e0229288.Otsuka S, Konno K, Abe M, Motohashi J, Kohda K, Sakimura K, Watanabe M, Yuzaki M: Roles of Cbln1 in Non-Motor Functions of Mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 2016, 36(46):11801-11816.
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NMDA-Rezeptor
NMDA receptor
Receptor NMDA
NMDA-reseptori
Récepteur NMDA
NMDA-receptor
NMDA-рецептор
NMDA reseptörü
