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Distinct G protein–coupled receptor recycling pathways allow spatial control of downstream G protein signaling
G protein–coupled receptors (GPCRs) are recycled via a sequence-dependent pathway that is spatially and biochemically distinct from bulk recycling. Why there are two distinct recycling pathways from the endosome is a fundamental question in cell biology. In this study, we show that the separation of...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037407/ https://www.ncbi.nlm.nih.gov/pubmed/27646272 http://dx.doi.org/10.1083/jcb.201512068 |
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author | Bowman, Shanna Lynn Shiwarski, Daniel John Puthenveedu, Manojkumar A. |
author_facet | Bowman, Shanna Lynn Shiwarski, Daniel John Puthenveedu, Manojkumar A. |
author_sort | Bowman, Shanna Lynn |
collection | PubMed |
description | G protein–coupled receptors (GPCRs) are recycled via a sequence-dependent pathway that is spatially and biochemically distinct from bulk recycling. Why there are two distinct recycling pathways from the endosome is a fundamental question in cell biology. In this study, we show that the separation of these two pathways is essential for normal spatial encoding of GPCR signaling. The prototypical β-2 adrenergic receptor (B2AR) activates Gα stimulatory protein (Gαs) on the endosome exclusively in sequence-dependent recycling tubules marked by actin/sorting nexin/retromer tubular (ASRT) microdomains. B2AR was detected in an active conformation in bulk recycling tubules, but was unable to activate Gαs. Protein kinase A phosphorylation of B2AR increases the fraction of receptors localized to ASRT domains and biases the downstream transcriptional effects of B2AR to genes controlled by endosomal signals. Our results identify the physiological relevance of separating GPCR recycling from bulk recycling and suggest a mechanism to tune downstream responses of GPCR signaling by manipulating the spatial origin of G protein signaling. |
format | Online Article Text |
id | pubmed-5037407 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-50374072017-03-26 Distinct G protein–coupled receptor recycling pathways allow spatial control of downstream G protein signaling Bowman, Shanna Lynn Shiwarski, Daniel John Puthenveedu, Manojkumar A. J Cell Biol Research Articles G protein–coupled receptors (GPCRs) are recycled via a sequence-dependent pathway that is spatially and biochemically distinct from bulk recycling. Why there are two distinct recycling pathways from the endosome is a fundamental question in cell biology. In this study, we show that the separation of these two pathways is essential for normal spatial encoding of GPCR signaling. The prototypical β-2 adrenergic receptor (B2AR) activates Gα stimulatory protein (Gαs) on the endosome exclusively in sequence-dependent recycling tubules marked by actin/sorting nexin/retromer tubular (ASRT) microdomains. B2AR was detected in an active conformation in bulk recycling tubules, but was unable to activate Gαs. Protein kinase A phosphorylation of B2AR increases the fraction of receptors localized to ASRT domains and biases the downstream transcriptional effects of B2AR to genes controlled by endosomal signals. Our results identify the physiological relevance of separating GPCR recycling from bulk recycling and suggest a mechanism to tune downstream responses of GPCR signaling by manipulating the spatial origin of G protein signaling. The Rockefeller University Press 2016-09-26 /pmc/articles/PMC5037407/ /pubmed/27646272 http://dx.doi.org/10.1083/jcb.201512068 Text en © 2016 Bowman et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Bowman, Shanna Lynn Shiwarski, Daniel John Puthenveedu, Manojkumar A. Distinct G protein–coupled receptor recycling pathways allow spatial control of downstream G protein signaling |
title | Distinct G protein–coupled receptor recycling pathways allow spatial control of downstream G protein signaling |
title_full | Distinct G protein–coupled receptor recycling pathways allow spatial control of downstream G protein signaling |
title_fullStr | Distinct G protein–coupled receptor recycling pathways allow spatial control of downstream G protein signaling |
title_full_unstemmed | Distinct G protein–coupled receptor recycling pathways allow spatial control of downstream G protein signaling |
title_short | Distinct G protein–coupled receptor recycling pathways allow spatial control of downstream G protein signaling |
title_sort | distinct g protein–coupled receptor recycling pathways allow spatial control of downstream g protein signaling |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037407/ https://www.ncbi.nlm.nih.gov/pubmed/27646272 http://dx.doi.org/10.1083/jcb.201512068 |
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