Signal Transduction
Orphan Receptor GPR158 Is an Allosteric Modulator of RGS7 Catalytic Activity with an Essential Role in Dictating Its Expression and Localization in the Brain
Regulators of G protein signaling control the duration and extent of signaling via G protein-coupled receptor (GPCR) pathways by accelerating the GTP hydrolysis on G protein α subunits thereby promoting termination of GPCR signaling. A member of this family, RGS7, plays a critical role in the nervous system where it regulates multiple neurotransmitter GPCRs that mediate vision, memory, and the action of addictive drugs. Previous studies have established that in vivo RGS7 forms mutually exclusive complexes with the membrane protein RGS7-binding protein or the orphan receptor GPR158.Evaluating the Role of Retinal Membrane Guanylyl Cyclase 1 (RetGC1) Domains in Binding Guanylyl Cyclase-activating Proteins (GCAPs)
Background: GCAP1 and GCAP2 regulate cGMP synthesis by RetGC1 in photoreceptors.Results: GCAPs compete for binding to RetGC1 in biochemical assays and in HEK293 cells co-expressing fluorescently labeled GCAPs with different forms of RetGC1.Conclusion: The GCAP1 and GCAP2 binding site(s) overlaps within the kinase homology and/or dimerization domains of RetGC1.Significance: RetGC1 and GCAPs contribute to normal vision and congenital blindness in humans.
