Beneath the surface: endosomal GPCR signaling

Trends Biochem Sci. 2024 Apr 19:S0968-0004(24)00072-0. doi: 10.1016/j.tibs.2024.03.006. Online ahead of print.ABSTRACTG protein-coupled receptors (GPCRs) located at the cell surface bind extracellular ligands and convey intracellular signals via activation of heterotrimeric G proteins. Traditionally, G protein signaling was viewed to occur exclusively at this subcellular region followed by rapid desensitization facilitated by β-arrestin (βarr)-mediated G protein uncoupling and receptor internalization. However, emerging evidence over the past 15 years suggests that these βarr-mediated events do not necessarily terminate receptor signaling and that some GPCRs continue to activate G proteins after having been internalized into endosomes. Here, we review the recently elucidated mechanistic basis underlying endosomal GPCR signaling and discuss physiological implications and pharmacological targeting of this newly appreciated signaling mode.PMID:38643023 | DOI:10.1016/j.tibs.2024.03.006

Source: Trends in Biochemical Sciences - April 20, 2024 Category: Biochemistry Authors: Emmanuel Flores-Espinoza Alex R B Thomsen Source Type: research