Cao Yan, Song Hongman, Okawa Haruhisa, Sampath Alapakkam P, Sokolov Maxim, Martemyanov Kirill A
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
J Neurosci. 2008 Oct 8;28(41):10443-9. doi: 10.1523/JNEUROSCI.3282-08.2008.
Complexes of regulator of G-protein signaling (RGS) proteins with G-protein beta5 (Gbeta5) subunits are essential components of signaling pathways that regulate the temporal characteristics of light-evoked responses in vertebrate retinal photoreceptors and ON-bipolar cells. Recent studies have found that RGS/Gbeta5 complexes bind to a new family of adapter proteins, R9AP (RGS9 anchor protein) and R7 family binding protein (R7BP), that in case of the RGS9/Gbeta5 complex were shown to determine its precise subcellular targeting to either the outer segment of photoreceptors or postsynaptic structures of striatal neurons, respectively. In this study, we establish that another trimeric complex consisting of RGS7, Gbeta5, and R7BP subunits is specifically targeted to the dendritic tips of retinal bipolar cells. However, examination of the mechanisms of complex targeting in vivo surprisingly revealed that the delivery of RGS7/Gbeta5 to the dendrites of ON-bipolar cells occurs independently of its association with R7BP. These findings provide a new mechanism for adapter-independent targeting of RGS/Gbeta5 complexes.
G蛋白信号调节因子(RGS)蛋白与G蛋白β5(Gβ5)亚基形成的复合物是信号通路的重要组成部分,这些信号通路调节脊椎动物视网膜光感受器和ON双极细胞中光诱发反应的时间特征。最近的研究发现,RGS/Gβ5复合物与一类新的衔接蛋白结合,即R9AP(RGS9锚定蛋白)和R7家族结合蛋白(R7BP),在RGS9/Gβ5复合物的情况下,分别显示出其精确的亚细胞定位,分别定位于光感受器的外段或纹状体神经元的突触后结构。在这项研究中,我们确定由RGS7、Gβ5和R7BP亚基组成的另一种三聚体复合物特异性定位于视网膜双极细胞的树突尖端。然而,对体内复合物靶向机制的研究令人惊讶地发现,RGS7/Gβ5向ON双极细胞树突的传递与其与R7BP的结合无关。这些发现为RGS/Gβ5复合物的非衔接蛋白依赖性靶向提供了一种新机制。