Fekete Christopher D, Goz Roman U, Dinallo Sean, Miralles Celia P, Chiou Tzu-Ting, Bear John, Fiondella Christopher G, LoTurco Joseph J, De Blas Angel L
Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, 06269.
J Comp Neurol. 2017 Apr 1;525(5):1291-1311. doi: 10.1002/cne.24137. Epub 2016 Nov 21.
Collybistin (CB) is a guanine nucleotide exchange factor selectively localized to γ-aminobutyric acid (GABA)ergic and glycinergic postsynapses. Active CB interacts with gephyrin, inducing the submembranous clustering and the postsynaptic accumulation of gephyrin, which is a scaffold protein that recruits GABA receptors (GABA Rs) at the postsynapse. CB is expressed with or without a src homology 3 (SH3) domain. We have previously reported the effects on GABAergic synapses of the acute overexpression of CB or CB in cultured hippocampal (HP) neurons. In the present communication, we are studying the effects on GABAergic synapses after chronic in vivo transgenic expression of CB2 or CB2 in neurons of the adult rat cerebral cortex. The embryonic precursors of these cortical neurons were in utero electroporated with CB or CB DNAs, migrated to the appropriate cortical layer, and became integrated in cortical circuits. The results show that: 1) the strength of inhibitory synapses in vivo can be enhanced by increasing the expression of CB in neurons; and 2) there are significant differences in the results between in vivo and in culture studies. J. Comp. Neurol. 525:1291-1311, 2017. © 2016 Wiley Periodicals, Inc.
结肠双调蛋白(CB)是一种鸟嘌呤核苷酸交换因子,选择性地定位于γ-氨基丁酸(GABA)能和甘氨酸能突触后膜。活性CB与桥连蛋白相互作用,诱导桥连蛋白在膜下聚集和突触后积累,桥连蛋白是一种在突触后募集GABA受体(GABA Rs)的支架蛋白。CB表达时带有或不带有src同源结构域3(SH3)。我们之前报道过在培养的海马(HP)神经元中急性过表达CB或CB对GABA能突触的影响。在本通讯中,我们正在研究成年大鼠大脑皮质神经元中慢性体内转基因表达CB2或CB2后对GABA能突触的影响。这些皮质神经元的胚胎前体细胞在子宫内用电穿孔法导入CB或CB DNA,迁移到适当的皮质层,并整合到皮质回路中。结果表明:1)通过增加神经元中CB的表达可以增强体内抑制性突触的强度;2)体内研究和培养研究的结果存在显著差异。《比较神经学杂志》525:1291 - 1311,2017年。©2016威利期刊公司。