Catalytic activation of β-arrestin by GPCRs

Kelsie Eichel, Damien Jullié, Benjamin Barsi-Rhyne, Naomi R. Latorraca, Matthieu Masureel, Jean-Baptiste Sibarita, Ron O. Dror and Mark Zastrow ()
Additional contact information
Kelsie Eichel: University of California, San Francisco School of Medicine
Damien Jullié: University of California, San Francisco School of Medicine
Benjamin Barsi-Rhyne: University of California, San Francisco School of Medicine
Naomi R. Latorraca: Stanford University
Matthieu Masureel: Stanford University School of Medicine
Jean-Baptiste Sibarita: Interdisciplinary Institute for Neuroscience, UMR 5297, Centre National de la Recherche Scientifique
Ron O. Dror: Stanford University
Mark Zastrow: University of California, San Francisco School of Medicine

Nature, 2018, vol. 557, issue 7705, 381-386

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41586-018-0079-1 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:557:y:2018:i:7705:d:10.1038_s41586-018-0079-1

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-018-0079-1

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().