The R7 RGS Protein Family: Multi-Subunit Regulators of Neuronal G Protein Signaling

Abstract

G protein-coupled receptor (GPCR) 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 Gβ5, 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.

Chronic exposure to cannabinoids during adolescence causes long‐lasting behavioral deficits in adult mice

“…(Holden et al , 2014; Kach et al , 2012). In particular, RGS7 plays key roles in the regulation of several biological processes such as vision, memory, motor control, reward behavior and nociception (Anderson et al , 2009; Orlandi et al , 2015). Although the mechanisms of this regulation remain to be elucidated, we demonstrated that long‐term administration of 3 mg/kg of WIN during mouse adolescence induces DNA hypermethylation at the intragenic Rgs7 region and concomitantly decreases the rate of transcription, potentially contributing at least in part to the learning and memory deficits as depicted in Fig.…”

Regulator of G Protein Signaling 6 (RGS6) Protein Ensures Coordination of Motor Movement by Modulating GABAB Receptor Signaling

“…Two additional domains unique to R7 family members, the GGL (G␥ subunit-like) domain and DEP/ DHEX domain, allow for complex formation between RGS6 and the accessory proteins G␤ 5 and R7BP, respectively. Binding to G␤ 5 results in stabilization of both proteins, whereas binding to R7BP is thought to primarily control the subcellular localization of R7 family members (18). R7 family RGS proteins have been implicated in controlling motor movement, because G␤ 5 Ϫ/Ϫ mice, which lack functional expression of all R7 family members (19), exhibit an ataxic phenotype likely due to abnormal cerebellar development (20,21).…”

Functional Mapping of Interacting Regions of the Photoreceptor Phosphodiesterase (PDE6) γ-Subunit with PDE6 Catalytic Dimer, Transducin, and Regulator of G-protein Signaling9–1 (RGS9–1)

“…This GTPase rate is determined by a complex of proteins that include T␣*-GTP, RGS9 -1, and other proteins (33); P␥ serves to facilitate the formation of a tighter complex of these proteins to potentiate the GTPase accelerating function of RGS9 -1 (34 -37). However, the interaction surface of P␥ with RGS9 -1 and the functional significance of the interactions are unclear.…”