Control of Gα<sub>q</sub> signaling dynamics and GPCR cross-talk by GRKs.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36427324.
- Also identified by DOI 10.1126/sciadv.abq3363 and PMC identifier 9699688.
- Licence recorded as CC BY-NC.
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Abstract
Numerous processes contribute to the regulation of G protein-coupled receptors (GPCRs), but relatively little is known about rapid mechanisms that control signaling on the seconds time scale or regulate cross-talk between receptors. Here, we reveal that the ability of some GPCR kinases (GRKs) to bind Gα<sub>q</sub> both drives acute signaling desensitization and regulates functional interactions between GPCRs. GRK2/3-mediated acute desensitization occurs within seconds, is rapidly reversible, and can occur upon local, subcellular activation. This rapid desensitization is kinase independent, insensitive to pharmacological inhibition, and generalizable across receptor families and effectors. We also find that the ability of GRK2 to bind G proteins also enables it to regulate the extent and timing of Gα<sub>q</sub>-dependent signaling cross-talk between GPCRs. Last, we find that G protein/GRK2 interactions enable a novel form of GPCR trafficking cross-talk. Together, this work reveals potent forms of Gα<sub>q</sub>-dependent GPCR regulation with wide-ranging pharmacological and physiological implications.