Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1752, USA.
J Neurochem. 2011 Nov;119(3):544-54. doi: 10.1111/j.1471-4159.2011.07457.x. Epub 2011 Sep 23.
Gβ5 is a divergent member of the signal-transducing G protein β subunit family encoded by GNB5 and expressed principally in brain and neuronal tissue. Among heterotrimeric Gβ isoforms, Gβ5 is unique in its ability to heterodimerize with members of the R7 subfamily of the regulator of G protein signaling proteins that contain G protein-γ like domains. Previous studies employing Gnb5 knockout (KO) mice have shown that Gβ5 is an essential stabilizer of such regulator of G protein signaling proteins and regulates the deactivation of retinal phototransduction and the proper functioning of retinal bipolar cells. However, little is known of the function of Gβ5 in the brain outside the visual system. We show here that mice lacking Gβ5 have a markedly abnormal neurologic phenotype that includes impaired development, tiptoe-walking, motor learning and coordination deficiencies, and hyperactivity. We further show that Gβ5-deficient mice have abnormalities of neuronal development in cerebellum and hippocampus. We find that the expression of both mRNA and protein from multiple neuronal genes is dysregulated in Gnb5 KO mice. Taken together with previous observations from Gnb5 KO mice, our findings suggest a model in which Gβ5 regulates dendritic arborization and/or synapse formation during development, in part by effects on gene expression.
Gβ5 是信号转导 G 蛋白β亚基家族的一个分支成员，由 GNB5 编码，主要表达于脑和神经元组织。在异源三聚体 Gβ 同型物中，Gβ5 独特之处在于能够与包含 G 蛋白-γ 样结构域的 G 蛋白信号转导调节蛋白 R7 亚家族成员形成异二聚体。先前采用 Gnb5 敲除（KO）小鼠的研究表明，Gβ5 是此类 G 蛋白信号转导调节蛋白的必需稳定剂，调节视网膜光转导的失活和视网膜双极细胞的正常功能。然而，对于 Gβ5 在视觉系统以外的大脑中的功能知之甚少。我们在这里表明，缺乏 Gβ5 的小鼠具有明显的神经表型异常，包括发育受损、踮脚行走、运动学习和协调缺陷以及过度活跃。我们进一步表明，缺乏 Gβ5 的小鼠在小脑和海马中有神经元发育异常。我们发现，Gnb5 KO 小鼠中的多种神经元基因的 mRNA 和蛋白表达均失调。结合 Gnb5 KO 小鼠的先前观察结果，我们的研究结果表明，Gβ5 通过对基因表达的影响，在发育过程中调节树突分支和/或突触形成的模型。
