Gβ3 is required for normal light ON responses and synaptic maintenance.
Gβ3 is required for normal light ON responses and synaptic maintenance.
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DOI：
10.1523/jneurosci.1436-12.2012
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发表时间：
2012-08-15
期刊：
影响因子：
--
通讯作者：
Vardi N
中科院分区：
文献类型：
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作者：
Dhingra A;Ramakrishnan H;Neinstein A;Fina ME;Xu Y;Li J;Chung DC;Lyubarsky A;Vardi N
异源三聚体G蛋白，包括Gα和Gβγ亚基，将代谢型受体偶联到各种下游效应物，并有助于组装和运输基于受体的信号传导复合物。Gβ3是一种G蛋白β亚基，在几种生理过程中起着关键作用，因为其基因的多态性与几种疾病的风险因素有关。视网膜ON双极细胞表达Gβ3，它们为研究其作用提供了一个极好的系统。在ON双极细胞中，mGluR6通过级联反应逆转光感受器的信号，其中从光感受器释放的谷氨酸关闭TRPM1通道。这种级联反应对视力至关重要，因为其蛋白质的缺乏会导致完全的先天性静止性夜盲症。在这里，我们报告说，Gβ3参与G蛋白异源三聚体耦合mGluR6 TRPM1。Gβ3基因缺失可使小鼠在暗视和明视条件下的光反应显著降低，但不能完全消除光反应，而且Gβ3基因缺失还可导致大多数级联反应元件和调节因子的错误定位和下调。此外，Gβ3可能在突触维持中起作用，因为在其缺失的情况下，内陷杆双极树突的数量大大减少，在发育期结束的3周时未观察到这种缺陷。
Heterotrimeric G-proteins, comprising Gα and Gβγ subunits, couple metabotropic receptors to various downstream effectors and contribute to assembling and trafficking receptor based signaling complexes. A G-protein β-subunit, Gβ3 plays a critical role in several physiological processes as a polymorphism in its gene is associated with a risk factor for several disorders. Retinal ON bipolar cells express Gβ3, and they provide an excellent system to study its role. In the ON bipolar cells, mGluR6 inverts the photoreceptor’s signal via a cascade in which glutamate released from photoreceptors closes the TRPM1 channel. This cascade is essential for vision since deficiencies in its proteins lead to complete congenital stationary night blindness. Here we report that Gβ3 participates in the G-protein heterotrimer that couples mGluR6 to TRPM1. Gβ3 deletion in mouse greatly reduces the light response under both scotopic and photopic conditions, but it does not eliminate it. In addition, Gβ3 deletion causes mislocalization and downregulation of most cascade elements and modulators. Furthermore, Gβ3 may play a role in synaptic maintenance since in its absence, the number of invaginating rod bipolar dendrites is greatly reduced, a deficit that was not observed at 3 weeks, the end of the developmental period.