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Smoothened determines β-arrestin–mediated removal of the G protein–coupled receptor Gpr161 from the primary cilium
Dynamic changes in membrane protein composition of the primary cilium are central to development and homeostasis, but we know little about mechanisms regulating membrane protein flux. Stimulation of the sonic hedgehog (Shh) pathway in vertebrates results in accumulation and activation of the effecto...
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/PMC4810300/ https://www.ncbi.nlm.nih.gov/pubmed/27002170 http://dx.doi.org/10.1083/jcb.201506132 |
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author | Pal, Kasturi Hwang, Sun-hee Somatilaka, Bandarigoda Badgandi, Hemant Jackson, Peter K. DeFea, Kathryn Mukhopadhyay, Saikat |
author_facet | Pal, Kasturi Hwang, Sun-hee Somatilaka, Bandarigoda Badgandi, Hemant Jackson, Peter K. DeFea, Kathryn Mukhopadhyay, Saikat |
author_sort | Pal, Kasturi |
collection | PubMed |
description | Dynamic changes in membrane protein composition of the primary cilium are central to development and homeostasis, but we know little about mechanisms regulating membrane protein flux. Stimulation of the sonic hedgehog (Shh) pathway in vertebrates results in accumulation and activation of the effector Smoothened within cilia and concomitant disappearance of a negative regulator, the orphan G protein–coupled receptor (GPCR), Gpr161. Here, we describe a two-step process determining removal of Gpr161 from cilia. The first step involves β-arrestin recruitment by the signaling competent receptor, which is facilitated by the GPCR kinase Grk2. An essential factor here is the ciliary trafficking and activation of Smoothened, which by increasing Gpr161–β-arrestin binding promotes Gpr161 removal, both during resting conditions and upon Shh pathway activation. The second step involves clathrin-mediated endocytosis, which functions outside of the ciliary compartment in coordinating Gpr161 removal. Mechanisms determining dynamic compartmentalization of Gpr161 in cilia define a new paradigm for down-regulation of GPCRs during developmental signaling from a specialized subcellular compartment. |
format | Online Article Text |
id | pubmed-4810300 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-48103002016-09-28 Smoothened determines β-arrestin–mediated removal of the G protein–coupled receptor Gpr161 from the primary cilium Pal, Kasturi Hwang, Sun-hee Somatilaka, Bandarigoda Badgandi, Hemant Jackson, Peter K. DeFea, Kathryn Mukhopadhyay, Saikat J Cell Biol Research Articles Dynamic changes in membrane protein composition of the primary cilium are central to development and homeostasis, but we know little about mechanisms regulating membrane protein flux. Stimulation of the sonic hedgehog (Shh) pathway in vertebrates results in accumulation and activation of the effector Smoothened within cilia and concomitant disappearance of a negative regulator, the orphan G protein–coupled receptor (GPCR), Gpr161. Here, we describe a two-step process determining removal of Gpr161 from cilia. The first step involves β-arrestin recruitment by the signaling competent receptor, which is facilitated by the GPCR kinase Grk2. An essential factor here is the ciliary trafficking and activation of Smoothened, which by increasing Gpr161–β-arrestin binding promotes Gpr161 removal, both during resting conditions and upon Shh pathway activation. The second step involves clathrin-mediated endocytosis, which functions outside of the ciliary compartment in coordinating Gpr161 removal. Mechanisms determining dynamic compartmentalization of Gpr161 in cilia define a new paradigm for down-regulation of GPCRs during developmental signaling from a specialized subcellular compartment. The Rockefeller University Press 2016-03-28 /pmc/articles/PMC4810300/ /pubmed/27002170 http://dx.doi.org/10.1083/jcb.201506132 Text en © 2016 Pal 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 Pal, Kasturi Hwang, Sun-hee Somatilaka, Bandarigoda Badgandi, Hemant Jackson, Peter K. DeFea, Kathryn Mukhopadhyay, Saikat Smoothened determines β-arrestin–mediated removal of the G protein–coupled receptor Gpr161 from the primary cilium |
title | Smoothened determines β-arrestin–mediated removal of the G protein–coupled receptor Gpr161 from the primary cilium |
title_full | Smoothened determines β-arrestin–mediated removal of the G protein–coupled receptor Gpr161 from the primary cilium |
title_fullStr | Smoothened determines β-arrestin–mediated removal of the G protein–coupled receptor Gpr161 from the primary cilium |
title_full_unstemmed | Smoothened determines β-arrestin–mediated removal of the G protein–coupled receptor Gpr161 from the primary cilium |
title_short | Smoothened determines β-arrestin–mediated removal of the G protein–coupled receptor Gpr161 from the primary cilium |
title_sort | smoothened determines β-arrestin–mediated removal of the g protein–coupled receptor gpr161 from the primary cilium |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810300/ https://www.ncbi.nlm.nih.gov/pubmed/27002170 http://dx.doi.org/10.1083/jcb.201506132 |
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