GPCR-G Protein-β-Arrestin Super-Complex Mediates Sustained G Protein Signaling.

ABSTRACT: Classically, G protein-coupled receptor (GPCR) stimulation promotes G protein signaling at the plasma membrane, followed by rapid β-arrestin-mediated desensitization and receptor internalization into endosomes. However, it has been demonstrated that some GPCRs activate G proteins from within internalized cellular compartments, resulting in sustained signaling. We have used a variety of biochemical, biophysical, and cell-based methods to demonstrate the existence, functionality, and architecture of internalized receptor complexes composed of a single GPCR, β-arrestin, and G protein. These super-complexes or "megaplexes" more readily form at receptors that interact strongly with β-arrestins via a C-terminal tail containing clusters of serine/threonine phosphorylation sites. Single-particle e

SUBMITTER: Thomsen ARB 

PROVIDER: S-EPMC5418658 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature