RGS7

RGS7, or regulator of G protein signaling 7, is a member of the R7 subfamily of the regulator of G protein signaling (RGS) proteins. It encodes a protein that functions as a GTPase-activating protein (GAP) for certain heterotrimeric G protein alpha subunits, thereby accelerating GTP hydrolysis and terminating G protein–coupled receptor (GPCR) signaling. RGS7 is widely studied for its role in modulating neuronal signaling pathways.

The R7 family proteins share a characteristic domain architecture that includes an N-terminal DEP domain, a G gamma-like (GGL) domain, and a C-terminal RGS domain. The GGL domain forms a obligate complex with the G protein subunit G beta5, stabilizing the RGS protein and guiding its function. Binding to R7BP (R7-binding protein) via the DEP domain influences the subcellular localization and stability of RGS7, promoting membrane association in neurons.

Functionally, RGS7 acts as a GAP for Gi/o family G alpha subunits, speeding up the return to the inactive GDP-bound state and thereby shaping the amplitude and duration of GPCR signaling. In neurons, RGS7 modulates signaling downstream of multiple receptors, including opioid and dopamine receptors, contributing to the regulation of synaptic transmission and neuronal excitability.

Expression of RGS7 is highest in the brain, with notable presence in cerebellar and forebrain regions, where it localizes to somatodendritic compartments and postsynaptic densities. Its activity is regulated by assembly into the RGS7–G beta5–R7BP complex, post-translational modifications, and interactions with other signaling proteins.

Clinical relevance is an area of ongoing research; alterations in RGS7 signaling are being investigated for potential roles in drug response and neuropsychiatric processes, though no definitive disease-causing mutations have been established.