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β-arrestin drives MAP kinase signaling from clathrin-coated structures after GPCR dissociation
β-arrestins critically regulate G protein-coupled receptor (GPCR) signaling, not only 'arresting' the G protein signal but also modulating endocytosis and initiating a discrete G protein-independent signal via MAP kinase(1–3). Despite enormous recent progress toward understanding biophysic...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767649/ https://www.ncbi.nlm.nih.gov/pubmed/26829388 http://dx.doi.org/10.1038/ncb3307 |
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author | Eichel, K. Jullié, D. von Zastrow, M. |
author_facet | Eichel, K. Jullié, D. von Zastrow, M. |
author_sort | Eichel, K. |
collection | PubMed |
description | β-arrestins critically regulate G protein-coupled receptor (GPCR) signaling, not only 'arresting' the G protein signal but also modulating endocytosis and initiating a discrete G protein-independent signal via MAP kinase(1–3). Despite enormous recent progress toward understanding biophysical aspects of arrestin function(4,5), its cell biology remains relatively poorly understood. Two key tenets underlie the present dogma: (1) β-arrestin accumulates in clathrin-coated structures (CCSs) exclusively in physical complex with its activating GPCR, and (2) MAP kinase activation requires endocytosis of formed GPCR - β-arrestin complexes(6–9). 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 signaling from CCSs. We propose a β-arrestin signaling cycle that is catalytically activated by the GPCR and energetically coupled to the endocytic machinery. |
format | Online Article Text |
id | pubmed-4767649 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-47676492016-08-01 β-arrestin drives MAP kinase signaling from clathrin-coated structures after GPCR dissociation Eichel, K. Jullié, D. von Zastrow, M. Nat Cell Biol Article β-arrestins critically regulate G protein-coupled receptor (GPCR) signaling, not only 'arresting' the G protein signal but also modulating endocytosis and initiating a discrete G protein-independent signal via MAP kinase(1–3). Despite enormous recent progress toward understanding biophysical aspects of arrestin function(4,5), its cell biology remains relatively poorly understood. Two key tenets underlie the present dogma: (1) β-arrestin accumulates in clathrin-coated structures (CCSs) exclusively in physical complex with its activating GPCR, and (2) MAP kinase activation requires endocytosis of formed GPCR - β-arrestin complexes(6–9). 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 signaling from CCSs. We propose a β-arrestin signaling cycle that is catalytically activated by the GPCR and energetically coupled to the endocytic machinery. 2016-02-01 2016-03 /pmc/articles/PMC4767649/ /pubmed/26829388 http://dx.doi.org/10.1038/ncb3307 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Eichel, K. Jullié, D. von Zastrow, M. β-arrestin drives MAP kinase signaling from clathrin-coated structures after GPCR dissociation |
title | β-arrestin drives MAP kinase signaling from clathrin-coated structures after GPCR dissociation |
title_full | β-arrestin drives MAP kinase signaling from clathrin-coated structures after GPCR dissociation |
title_fullStr | β-arrestin drives MAP kinase signaling from clathrin-coated structures after GPCR dissociation |
title_full_unstemmed | β-arrestin drives MAP kinase signaling from clathrin-coated structures after GPCR dissociation |
title_short | β-arrestin drives MAP kinase signaling from clathrin-coated structures after GPCR dissociation |
title_sort | β-arrestin drives map kinase signaling from clathrin-coated structures after gpcr dissociation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767649/ https://www.ncbi.nlm.nih.gov/pubmed/26829388 http://dx.doi.org/10.1038/ncb3307 |
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