부산대학교 도서관

[beta]-arrestins are critical regulator and transducer proteins for G-protein-coupled receptors (GPCRs). [beta]-arrestin is widely believed to be activated by forming a stable and stoichiometric GPCR-[beta]-arrestin scaffold complex, which requires and is driven by the phosphorylated tail of the GPCR. Here we demonstrate a distinct and additional mechanism of [beta]-arrestin activation that does not require stable GPCR-[beta]-arrestin scaffolding or the GPCR tail. Instead, it occurs through transient engagement of the GPCR core, which destabilizes a conserved inter-domain charge network in [beta]-arrestin. This promotes capture of [beta]-arrestin at the plasma membrane and its accumulation in clathrin-coated endocytic structures (CCSs) after dissociation from the GPCR, requiring a series of interactions with membrane phosphoinositides and CCS-lattice proteins. [beta]-arrestin clustering in CCSs in the absence of the upstream activating GPCR is associated with a [beta]-arrestin-dependent component of the cellular ERK (extracellular signal-regulated kinase) response. These results delineate a discrete mechanism of cellular [beta]-arrestin function that is activated catalytically by GPCRs.Transient engagement of the G protein-coupled receptor core can act as a catalyst to activate cellular [beta]-arrestin function after dissociation from the receptor.
Author(s): Kelsie Eichel [sup.1] [sup.2] , Damien Jullié [sup.1] [sup.2] , Benjamin Barsi-Rhyne [sup.1] [sup.2] , Naomi R. Latorraca [sup.3] [sup.4] [sup.5] [sup.6] , Matthieu Masureel [sup.5] , Jean-Baptiste Sibarita [...]