The interaction, mechanism and function of GPR158-RGS7 cross-talk.

GPR158 is an orphan G protein-coupled receptor (GPCR) that is broadly expressed in the brain and displays unique structural characteristics and signaling mechanisms. GPR158 is a binding partner for the regulator of G protein signaling 7 (RGS7) and augments its expression, subcellular localization, and catalytic activity. Recent cryo-electron microscopy (cryo-EM) studies have revealed the structure of GPR158 alone and in complex with RGS7. The GPR158-RGS7 complex is shown to be regulated by chronic stress exposure and is a modulator of stress-induced depression. This review highlights the signaling mechanism and function of GPR158-RGS7 and provides a context for the unique formation of GPCR-RGS complexes.