Opioid receptors reveal a discrete cellular mechanism of endosomal G protein activation.

ABSTRACT: Many GPCRs initiate a second phase of G protein-mediated signaling from endosomes, which inherently requires an increase in G protein activity on the endosome surface. G_s-coupled GPCRs are thought to achieve this by internalizing and allosterically activating cognate G proteins again on the endosome membrane. Here we demonstrate that the μ-opioid receptor (MOR), a G_i-coupled GPCR, increases endosomal G protein activity in a different way. Leveraging conformational biosensors, we resolve the subcellular activation dynamics of endogenously expressed MOR and G_i/o-subclass G proteins. We show that MOR activation triggers a transient increase of active-state G_i/o on the plasma membrane that is followed by a prolonged increase on endosomes. Contrary to

SUBMITTER: Fisher NM 

PROVIDER: S-EPMC11482822 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature