Anderson Garret R, Posokhova Ekaterina, Martemyanov Kirill A
Department of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455, USA.
Cell Biochem Biophys. 2009;54(1-3):33-46. doi: 10.1007/s12013-009-9052-9. Epub 2009 Jun 12.
G protein-coupled receptor signaling pathways mediate the transmission of signals from the extracellular environment to the generation of cellular responses, a process that is critically important for neurons and neurotransmitter action. The ability to promptly respond to rapidly changing stimulation requires timely inactivation of G proteins, a process controlled by a family of specialized proteins known as regulators of G protein signaling (RGS). The R7 group of RGS proteins (R7 RGS) has received special attention due to their pivotal roles in the regulation of a range of crucial neuronal processes such as vision, motor control, reward behavior, and nociception in mammals. Four proteins in this group, RGS6, RGS7, RGS9, and RGS11, share a common molecular organization of three modules: (i) the catalytic RGS domain, (ii) a GGL domain that recruits G beta(5), an outlying member of the G protein beta subunit family, and (iii) a DEP/DHEX domain that mediates interactions with the membrane anchor proteins R7BP and R9AP. As heterotrimeric complexes, R7 RGS proteins not only associate with and regulate a number of G protein signaling pathway components, but have also been found to form complexes with proteins that are not traditionally associated with G protein signaling. This review summarizes our current understanding of the biology of the R7 RGS complexes including their structure/functional organization, protein-protein interactions, and physiological roles.
G蛋白偶联受体信号通路介导从细胞外环境到细胞反应产生的信号传递，这一过程对神经元和神经递质作用至关重要。要对快速变化的刺激做出及时反应，就需要G蛋白及时失活，这一过程由一类称为G蛋白信号调节剂（RGS）的特殊蛋白质所控制。RGS蛋白的R7亚组（R7 RGS）因其在调节一系列关键神经元过程（如哺乳动物的视觉、运动控制、奖赏行为和痛觉感受）中的关键作用而受到特别关注。该亚组中的四种蛋白质，即RGS6、RGS7、RGS9和RGS11，具有共同的分子结构，由三个模块组成：（i）催化性RGS结构域，（ii）招募Gβ5（G蛋白β亚基家族的一个外围成员）的GGL结构域，以及（iii）介导与膜锚定蛋白R7BP和R9AP相互作用的DEP/DHEX结构域。作为异源三聚体复合物，R7 RGS蛋白不仅与许多G蛋白信号通路成分结合并对其进行调节，还被发现与传统上不与G蛋白信号相关的蛋白质形成复合物。本综述总结了我们目前对R7 RGS复合物生物学的理解，包括其结构/功能组织、蛋白质-蛋白质相互作用和生理作用。
