Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1784593325465010176 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8562845 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT anwarmumtaz tyrosinephosphorylationofs1pr1leadstochaperonebipmediatedimporttotheendoplasmicreticulum AT aminmdruhul tyrosinephosphorylationofs1pr1leadstochaperonebipmediatedimporttotheendoplasmicreticulum AT balajiragunathraovijayavin tyrosinephosphorylationofs1pr1leadstochaperonebipmediatedimporttotheendoplasmicreticulum AT matschejacob tyrosinephosphorylationofs1pr1leadstochaperonebipmediatedimporttotheendoplasmicreticulum AT karginovandrei tyrosinephosphorylationofs1pr1leadstochaperonebipmediatedimporttotheendoplasmicreticulum AT minshallrichardd tyrosinephosphorylationofs1pr1leadstochaperonebipmediatedimporttotheendoplasmicreticulum AT mogarych tyrosinephosphorylationofs1pr1leadstochaperonebipmediatedimporttotheendoplasmicreticulum AT komarovayulia tyrosinephosphorylationofs1pr1leadstochaperonebipmediatedimporttotheendoplasmicreticulum AT mehtadolly tyrosinephosphorylationofs1pr1leadstochaperonebipmediatedimporttotheendoplasmicreticulum |