Retina-specific GTPase accelerator RGS11/G beta 5S/R9AP is a constitutive heterotrimer selectively targeted to mGluR6 in ON-bipolar neurons.
Retina-specific GTPase accelerator RGS11/G beta 5S/R9AP is a constitutive heterotrimer selectively targeted to mGluR6 in ON-bipolar neurons.
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DOI：
10.1523/jneurosci.1367-09.2009
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发表时间：
2009-07-22
期刊：
影响因子：
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通讯作者：
Martemyanov KA
中科院分区：
文献类型：
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作者：
Cao Y;Masuho I;Okawa H;Xie K;Asami J;Kammermeier PJ;Maddox DM;Furukawa T;Inoue T;Sampath AP;Martemyanov KA
G 蛋白信号调节蛋白 (R7 RGS) 蛋白 R7 家族的成员形成多亚基复合物，在处理视网膜神经元的光反应中发挥着至关重要的作用。这些复合物的破坏已被证明会导致视网膜光感受器时间分辨率的丧失以及向下游神经元的突触传递不足。尽管该家族的一个成员 RGS9-1 在控制脊椎动物光转导中的作用已得到充分证实，但人们对视网膜中其他成员的作用和组织原理知之甚少。在这里，我们研究了包含 RGS11（RGS9-1 最接近的同源物）的复合物的组成、定位和功能。我们发现 RGS11 与 5 型 G 蛋白 β 亚基 (Gβ5) 的短剪接亚型和 RGS9 锚定蛋白 (R9AP) 形成一种新型的必需三聚复合物。该复合物仅在 ON-双极细胞的树突尖端表达，其定位是通过与 mGluR6（ON-双极光响应所必需的谷氨酸受体）直接关联来实现的。虽然与 R9AP 和 mGluR6 的结合有助于复合物的蛋白水解稳定，但 RGS11 的突触后靶向并非由其膜锚定 R9AP 决定。小鼠视杆 ON-双极细胞中光反应的电生理记录表明，RGS11 的遗传消除对暗适应细胞中或适应背景光过程中 Gαo 的失活几乎没有影响。这些结果表明光响应期间 mGluR6 级联的失活可能需要多种 GTP 酶激活蛋白的贡献。
Members of the R7 family of the Regulators of G protein signaling (R7 RGS) proteins form multi-subunit complexes that play crucial roles in processing the light responses of retinal neurons. The disruption of these complexes has been shown to lead to the loss of temporal resolution in retinal photoreceptors and deficient synaptic transmission to downstream neurons. Despite the well established role of one member of this family, RGS9-1, in controlling vertebrate phototransduction, the roles and organizational principles of other members in the retina are poorly understood. Here we investigate the composition, localization, and function of complexes containing RGS11, the closest homolog of RGS9-1. We find that RGS11 forms a novel obligatory trimeric complex with the short splice isoform of the type 5 G protein β subunit (Gβ5), and the RGS9 Anchor Protein (R9AP). The complex is expressed exclusively in the dendritic tips of ON-bipolar cells where its localization is accomplished through a direct association with mGluR6, the glutamate receptor essential for the ON-bipolar light response. While association with both R9AP and mGluR6 contributed to the proteolytic stabilization of the complex, postsynaptic targeting of RGS11 was not determined by its membrane anchor, R9AP. Electrophysiological recordings of the light response in mouse rod ON-bipolar cells reveal that the genetic elimination of RGS11 has little effect on the deactivation of Gαo in dark-adapted cells or during adaptation to background light. These results suggest the deactivation of mGluR6 cascade during the light response may require the contribution of multiple GTPase activating proteins.