β-Arrestin drives MAP kinase signalling from clathrin-coated structures after GPCR dissociation
| Autor: | Kelsie Eichel, M von Zastrow, Damien Jullié |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
genetic structures Arrestins Endocytic cycle Biology Endocytosis Clathrin Article Cell Line Receptors G-Protein-Coupled 03 medical and health sciences 0302 clinical medicine GTP-binding protein regulators GTP-Binding Proteins Arrestin Animals Humans beta-Arrestins G protein-coupled receptor Beta-Arrestins Cell Biology beta-Arrestin 2 eye diseases Cell biology 030104 developmental biology biology.protein sense organs Signal transduction Mitogen-Activated Protein Kinases 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Nature cell biology |
| ISSN: | 1476-4679 |
| Popis: | β-Arrestins critically regulate G-protein-coupled receptor (GPCR) signalling, not only 'arresting' the G protein signal but also modulating endocytosis and initiating a discrete G-protein-independent signal through MAP kinase. Despite enormous recent progress towards understanding biophysical aspects of arrestin function, arrestin cell biology remains relatively poorly understood. Two key tenets underlie the prevailing current view: β-arrestin accumulates in clathrin-coated structures (CCSs) exclusively in physical complex with its activating GPCR, and MAP kinase activation requires endocytosis of formed GPCR-β-arrestin complexes. We show here, using β1-adrenergic receptors, that β-arrestin-2 (arrestin 3) accumulates robustly in CCSs after dissociating from its activating GPCR and transduces the MAP kinase signal from CCSs. Moreover, inhibiting subsequent endocytosis of CCSs enhances the clathrin- and β-arrestin-dependent MAP kinase signal. These results demonstrate β-arrestin 'activation at a distance', after dissociating from its activating GPCR, and signalling from CCSs. We propose a β-arrestin signalling cycle that is catalytically activated by the GPCR and energetically coupled to the endocytic machinery. |
| Databáze: | OpenAIRE |
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