Abstract：
:β-arrestins are critical regulator and transducer proteins for G-protein-coupled receptors (GPCRs). β-arrestin is widely believed to be activated by forming a stable and stoichiometric GPCR-β-arrestin scaffold complex, which requires and is driven by the phosphorylated tail of the GPCR. Here we demonstrate a distinct and additional mechanism of β-arrestin activation that does not require stable GPCR-β-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 β-arrestin. This promotes capture of β-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. β-arrestin clustering in CCSs in the absence of the upstream activating GPCR is associated with a β-arrestin-dependent component of the cellular ERK (extracellular signal-regulated kinase) response. These results delineate a discrete mechanism of cellular β-arrestin function that is activated catalytically by GPCRs.
journal_name
Naturejournal_title
Natureauthors
Eichel K,Jullié D,Barsi-Rhyne B,Latorraca NR,Masureel M,Sibarita JB,Dror RO,von Zastrow Mdoi
10.1038/s41586-018-0079-1subject
Has Abstractpub_date
2018-05-01 00:00:00pages
381-386issue
7705eissn
0028-0836issn
1476-4687pii
10.1038/s41586-018-0079-1journal_volume
557pub_type
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