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Tyrosine phosphorylation of S1PR1 leads to chaperone BiP-mediated import to the endoplasmic reticulum

Cell surface G protein–coupled receptors (GPCRs), upon agonist binding, undergo serine–threonine phosphorylation, leading to either receptor recycling or degradation. Here, we show a new fate of GPCRs, exemplified by ER retention of sphingosine-1-phosphate receptor 1 (S1PR1). We show that S1P phosph...

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Autores principales: Anwar, Mumtaz, Amin, Md Ruhul, Balaji Ragunathrao, Vijay Avin, Matsche, Jacob, Karginov, Andrei, Minshall, Richard D., Mo, Gary C.H., Komarova, Yulia, Mehta, Dolly
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8562845/
https://www.ncbi.nlm.nih.gov/pubmed/34652421
http://dx.doi.org/10.1083/jcb.202006021
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author Anwar, Mumtaz
Amin, Md Ruhul
Balaji Ragunathrao, Vijay Avin
Matsche, Jacob
Karginov, Andrei
Minshall, Richard D.
Mo, Gary C.H.
Komarova, Yulia
Mehta, Dolly
author_facet Anwar, Mumtaz
Amin, Md Ruhul
Balaji Ragunathrao, Vijay Avin
Matsche, Jacob
Karginov, Andrei
Minshall, Richard D.
Mo, Gary C.H.
Komarova, Yulia
Mehta, Dolly
author_sort Anwar, Mumtaz
collection PubMed
description Cell surface G protein–coupled receptors (GPCRs), upon agonist binding, undergo serine–threonine phosphorylation, leading to either receptor recycling or degradation. Here, we show a new fate of GPCRs, exemplified by ER retention of sphingosine-1-phosphate receptor 1 (S1PR1). We show that S1P phosphorylates S1PR1 on tyrosine residue Y(143), which is associated with recruitment of activated BiP from the ER into the cytosol. BiP then interacts with endocytosed Y(143)-S1PR1 and delivers it into the ER. In contrast to WT-S1PR1, which is recycled and stabilizes the endothelial barrier, phosphomimicking S1PR1 (Y(143)D-S1PR1) is retained by BiP in the ER and increases cytosolic Ca(2+) and disrupts barrier function. Intriguingly, a proinflammatory, but non-GPCR agonist, TNF-α, also triggered barrier-disruptive signaling by promoting S1PR1 phosphorylation on Y(143) and its import into ER via BiP. BiP depletion restored Y(143)D-S1PR1 expression on the endothelial cell surface and rescued canonical receptor functions. Findings identify Y(143)-phosphorylated S1PR1 as a potential target for prevention of endothelial barrier breakdown under inflammatory conditions.
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spelling pubmed-85628452022-06-06 Tyrosine phosphorylation of S1PR1 leads to chaperone BiP-mediated import to the endoplasmic reticulum Anwar, Mumtaz Amin, Md Ruhul Balaji Ragunathrao, Vijay Avin Matsche, Jacob Karginov, Andrei Minshall, Richard D. Mo, Gary C.H. Komarova, Yulia Mehta, Dolly J Cell Biol Article Cell surface G protein–coupled receptors (GPCRs), upon agonist binding, undergo serine–threonine phosphorylation, leading to either receptor recycling or degradation. Here, we show a new fate of GPCRs, exemplified by ER retention of sphingosine-1-phosphate receptor 1 (S1PR1). We show that S1P phosphorylates S1PR1 on tyrosine residue Y(143), which is associated with recruitment of activated BiP from the ER into the cytosol. BiP then interacts with endocytosed Y(143)-S1PR1 and delivers it into the ER. In contrast to WT-S1PR1, which is recycled and stabilizes the endothelial barrier, phosphomimicking S1PR1 (Y(143)D-S1PR1) is retained by BiP in the ER and increases cytosolic Ca(2+) and disrupts barrier function. Intriguingly, a proinflammatory, but non-GPCR agonist, TNF-α, also triggered barrier-disruptive signaling by promoting S1PR1 phosphorylation on Y(143) and its import into ER via BiP. BiP depletion restored Y(143)D-S1PR1 expression on the endothelial cell surface and rescued canonical receptor functions. Findings identify Y(143)-phosphorylated S1PR1 as a potential target for prevention of endothelial barrier breakdown under inflammatory conditions. Rockefeller University Press 2021-10-15 /pmc/articles/PMC8562845/ /pubmed/34652421 http://dx.doi.org/10.1083/jcb.202006021 Text en © 2021 Anwar et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/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 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Anwar, Mumtaz
Amin, Md Ruhul
Balaji Ragunathrao, Vijay Avin
Matsche, Jacob
Karginov, Andrei
Minshall, Richard D.
Mo, Gary C.H.
Komarova, Yulia
Mehta, Dolly
Tyrosine phosphorylation of S1PR1 leads to chaperone BiP-mediated import to the endoplasmic reticulum
title Tyrosine phosphorylation of S1PR1 leads to chaperone BiP-mediated import to the endoplasmic reticulum
title_full Tyrosine phosphorylation of S1PR1 leads to chaperone BiP-mediated import to the endoplasmic reticulum
title_fullStr Tyrosine phosphorylation of S1PR1 leads to chaperone BiP-mediated import to the endoplasmic reticulum
title_full_unstemmed Tyrosine phosphorylation of S1PR1 leads to chaperone BiP-mediated import to the endoplasmic reticulum
title_short Tyrosine phosphorylation of S1PR1 leads to chaperone BiP-mediated import to the endoplasmic reticulum
title_sort tyrosine phosphorylation of s1pr1 leads to chaperone bip-mediated import to the endoplasmic reticulum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8562845/
https://www.ncbi.nlm.nih.gov/pubmed/34652421
http://dx.doi.org/10.1083/jcb.202006021
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