Membrane curvature association of amphipathic helix 8 drives constitutive endocytosis of GPCRs.

ABSTRACT: Cellular signaling relies on the activity of transmembrane receptors and their presentation on the cellular surface. Their continuous insertion in the plasma membrane is balanced by constitutive and activity-dependent internalization, which is orchestrated by adaptor proteins recognizing semispecific motifs within the receptors' intracellular regions. Here, we describe a complementary trafficking mechanism for G protein-coupled receptors (GPCRs) that is evolutionary conserved and refined. This mechanism relies on the insertion of their amphipathic helix 8 into the inner leaflet of lipid membranes, orthogonal to the transmembrane helices. These amphipathic helices dictate subcellular localization of the receptors and autonomously drive their endocytosis by cooperative assembly and associati

SUBMITTER: Schmidt JH 

PROVIDER: S-EPMC12346279 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature