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The ubiquitin ligase deltex-3l regulates endosomal sorting of the G protein–coupled receptor CXCR4

G protein–coupled receptor (GPCR) sorting into the degradative pathway is important for limiting the duration and magnitude of signaling. Agonist activation of the GPCR CXCR4 induces its rapid ubiquitination and sorting to lysosomes via the endosomal sorting complex required for transport (ESCRT) pa...

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Autores principales: Holleman, Justine, Marchese, Adriano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055268/
https://www.ncbi.nlm.nih.gov/pubmed/24790097
http://dx.doi.org/10.1091/mbc.E13-10-0612
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author Holleman, Justine
Marchese, Adriano
author_facet Holleman, Justine
Marchese, Adriano
author_sort Holleman, Justine
collection PubMed
description G protein–coupled receptor (GPCR) sorting into the degradative pathway is important for limiting the duration and magnitude of signaling. Agonist activation of the GPCR CXCR4 induces its rapid ubiquitination and sorting to lysosomes via the endosomal sorting complex required for transport (ESCRT) pathway. We recently reported that ESCRT-0 ubiquitination is linked to the efficiency with which CXCR4 is sorted for lysosomal degradation; however mechanistic insight is lacking. Here we define a novel role for the really interesting new gene–domain E3 ubiquitin ligase deltex-3-like (DTX3L) in regulating CXCR4 sorting from endosomes to lysosomes. We show that DTX3L localizes to early endosomes upon CXCR4 activation and interacts directly with and inhibits the activity of the E3 ubiquitin ligase atrophin-1 interacting protein 4. This serves to limit the extent to which ESCRT-0 is ubiquitinated and is able to sort CXCR4 for lysosomal degradation. Therefore we define a novel role for DTX3L in GPCR endosomal sorting and reveal an unprecedented link between two distinct E3 ubiquitin ligases to control the activity of the ESCRT machinery.
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spelling pubmed-40552682014-08-30 The ubiquitin ligase deltex-3l regulates endosomal sorting of the G protein–coupled receptor CXCR4 Holleman, Justine Marchese, Adriano Mol Biol Cell Articles G protein–coupled receptor (GPCR) sorting into the degradative pathway is important for limiting the duration and magnitude of signaling. Agonist activation of the GPCR CXCR4 induces its rapid ubiquitination and sorting to lysosomes via the endosomal sorting complex required for transport (ESCRT) pathway. We recently reported that ESCRT-0 ubiquitination is linked to the efficiency with which CXCR4 is sorted for lysosomal degradation; however mechanistic insight is lacking. Here we define a novel role for the really interesting new gene–domain E3 ubiquitin ligase deltex-3-like (DTX3L) in regulating CXCR4 sorting from endosomes to lysosomes. We show that DTX3L localizes to early endosomes upon CXCR4 activation and interacts directly with and inhibits the activity of the E3 ubiquitin ligase atrophin-1 interacting protein 4. This serves to limit the extent to which ESCRT-0 is ubiquitinated and is able to sort CXCR4 for lysosomal degradation. Therefore we define a novel role for DTX3L in GPCR endosomal sorting and reveal an unprecedented link between two distinct E3 ubiquitin ligases to control the activity of the ESCRT machinery. The American Society for Cell Biology 2014-06-15 /pmc/articles/PMC4055268/ /pubmed/24790097 http://dx.doi.org/10.1091/mbc.E13-10-0612 Text en © 2014 Holleman and Marchese. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Holleman, Justine
Marchese, Adriano
The ubiquitin ligase deltex-3l regulates endosomal sorting of the G protein–coupled receptor CXCR4
title The ubiquitin ligase deltex-3l regulates endosomal sorting of the G protein–coupled receptor CXCR4
title_full The ubiquitin ligase deltex-3l regulates endosomal sorting of the G protein–coupled receptor CXCR4
title_fullStr The ubiquitin ligase deltex-3l regulates endosomal sorting of the G protein–coupled receptor CXCR4
title_full_unstemmed The ubiquitin ligase deltex-3l regulates endosomal sorting of the G protein–coupled receptor CXCR4
title_short The ubiquitin ligase deltex-3l regulates endosomal sorting of the G protein–coupled receptor CXCR4
title_sort ubiquitin ligase deltex-3l regulates endosomal sorting of the g protein–coupled receptor cxcr4
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055268/
https://www.ncbi.nlm.nih.gov/pubmed/24790097
http://dx.doi.org/10.1091/mbc.E13-10-0612
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