Imboden M, De Saint Jan D, Leulier F, Korn H, Goblet C, Bregestovski P
Laboratoire de Biologie Cellulaire et Moléculaire du Neurone, INSERM U261, Institut Pasteur, 25, Rue du Dr Roux, F-75724, Paris Cedex 15, France.
Neuroscience. 2001;103(3):799-810. doi: 10.1016/s0306-4522(00)00575-3.
The complementary DNA for a novel alpha subunit of the glycine receptor, alphaZ2, was isolated from a zebrafish adult brain library. The molecular characteristics, phylogenetic relationships and messenger RNA length of this alphaZ2 subunit show it to be an alpha2-type glycine receptor subunit isoform. The leader peptide however, diverges from those of known glycine receptor alpha isoforms. Recombinantly expressed in Xenopus oocytes, alphaZ2 formed functional glycine receptor channels. These homomeric channels were activated by glycine and taurine, with apparent affinities similar to those reported for zebrafish alphaZ1 glycine receptor, and were also effectively antagonized by nanomolar concentrations of strychnine. However, during prolonged applications of agonists, ionic currents of alphaZ2 receptor channels declined to a much lower steady-state level than those of alphaZ1, indicating different desensitization properties. Analysis of messenger RNA revealed that alphaZ2 is specifically expressed in adult brain tissue and present in both adult and embryonic zebrafish. This report contributes to the characterization of the diversity of glycine receptor isoforms in vertebrates.
从斑马鱼成体脑文库中分离出甘氨酸受体新型α亚基αZ2的互补DNA。该αZ2亚基的分子特征、系统发育关系及信使RNA长度表明它是一种α2型甘氨酸受体亚基异构体。然而，其前导肽与已知的甘氨酸受体α异构体不同。αZ2在非洲爪蟾卵母细胞中重组表达时，形成了功能性甘氨酸受体通道。这些同聚体通道可被甘氨酸和牛磺酸激活，其表观亲和力与报道的斑马鱼αZ1甘氨酸受体相似，且也能被纳摩尔浓度的士的宁有效拮抗。然而，在长时间应用激动剂时，αZ2受体通道的离子电流下降至比αZ1低得多的稳态水平，表明其脱敏特性不同。信使RNA分析显示，αZ2在成体脑组织中特异性表达，且在成年和胚胎斑马鱼中均有存在。本报告有助于对脊椎动物中甘氨酸受体异构体多样性的表征。
