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SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways

The FERM-like domain–containing sorting nexins of the SNX17/SNX27/SNX31 family have been proposed to mediate retrieval of transmembrane proteins from the lysosomal pathway. In this paper, we describe a stable isotope labeling with amino acids in culture–based quantitative proteomic approach that all...

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Autores principales: Steinberg, Florian, Heesom, Kate J., Bass, Mark D., Cullen, Peter J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328392/
https://www.ncbi.nlm.nih.gov/pubmed/22492727
http://dx.doi.org/10.1083/jcb.201111121
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author Steinberg, Florian
Heesom, Kate J.
Bass, Mark D.
Cullen, Peter J.
author_facet Steinberg, Florian
Heesom, Kate J.
Bass, Mark D.
Cullen, Peter J.
author_sort Steinberg, Florian
collection PubMed
description The FERM-like domain–containing sorting nexins of the SNX17/SNX27/SNX31 family have been proposed to mediate retrieval of transmembrane proteins from the lysosomal pathway. In this paper, we describe a stable isotope labeling with amino acids in culture–based quantitative proteomic approach that allows an unbiased, global identification of transmembrane cargoes that are rescued from lysosomal degradation by SNX17. This screen revealed that several integrins required SNX17 for their stability, as depletion of SNX17 led to a loss of β1 and β5 integrins and associated a subunits from HeLa cells as a result of increased lysosomal degradation. SNX17 bound to the membrane distal NPXY motif in β integrin cytoplasmic tails, thereby preventing lysosomal degradation of β integrins and their associated a subunits. Furthermore, SNX17-dependent retrieval of integrins did not depend on the retromer complex. Consistent with an effect on integrin recycling, depletion of SNX17 also caused alterations in cell migration. Our data provide mechanistic insight into the retrieval of internalized integrins from the lysosomal degradation pathway, a prerequisite for subsequent recycling of these matrix receptors.
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spelling pubmed-33283922012-10-16 SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways Steinberg, Florian Heesom, Kate J. Bass, Mark D. Cullen, Peter J. J Cell Biol Research Articles The FERM-like domain–containing sorting nexins of the SNX17/SNX27/SNX31 family have been proposed to mediate retrieval of transmembrane proteins from the lysosomal pathway. In this paper, we describe a stable isotope labeling with amino acids in culture–based quantitative proteomic approach that allows an unbiased, global identification of transmembrane cargoes that are rescued from lysosomal degradation by SNX17. This screen revealed that several integrins required SNX17 for their stability, as depletion of SNX17 led to a loss of β1 and β5 integrins and associated a subunits from HeLa cells as a result of increased lysosomal degradation. SNX17 bound to the membrane distal NPXY motif in β integrin cytoplasmic tails, thereby preventing lysosomal degradation of β integrins and their associated a subunits. Furthermore, SNX17-dependent retrieval of integrins did not depend on the retromer complex. Consistent with an effect on integrin recycling, depletion of SNX17 also caused alterations in cell migration. Our data provide mechanistic insight into the retrieval of internalized integrins from the lysosomal degradation pathway, a prerequisite for subsequent recycling of these matrix receptors. The Rockefeller University Press 2012-04-16 /pmc/articles/PMC3328392/ /pubmed/22492727 http://dx.doi.org/10.1083/jcb.201111121 Text en © 2012 Steinberg 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
Steinberg, Florian
Heesom, Kate J.
Bass, Mark D.
Cullen, Peter J.
SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways
title SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways
title_full SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways
title_fullStr SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways
title_full_unstemmed SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways
title_short SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways
title_sort snx17 protects integrins from degradation by sorting between lysosomal and recycling pathways
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328392/
https://www.ncbi.nlm.nih.gov/pubmed/22492727
http://dx.doi.org/10.1083/jcb.201111121
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