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Virus Control of Trafficking from Sorting Endosomes
The maintenance of cell surface proteins is critical to the ability of a cell to sense and respond to information in its environment. As such, modulation of cell surface composition and receptor trafficking is a potentially important target of control in virus infection. Sorting endosomes (SEs) are...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058287/ https://www.ncbi.nlm.nih.gov/pubmed/30042195 http://dx.doi.org/10.1128/mBio.00683-18 |
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author | Zeltzer, Sebastian Zeltzer, Carol A. Igarashi, Suzu Wilson, Jean Donaldson, Julie G. Goodrum, Felicia |
author_facet | Zeltzer, Sebastian Zeltzer, Carol A. Igarashi, Suzu Wilson, Jean Donaldson, Julie G. Goodrum, Felicia |
author_sort | Zeltzer, Sebastian |
collection | PubMed |
description | The maintenance of cell surface proteins is critical to the ability of a cell to sense and respond to information in its environment. As such, modulation of cell surface composition and receptor trafficking is a potentially important target of control in virus infection. Sorting endosomes (SEs) are control stations regulating the recycling or degradation of internalized plasma membrane proteins. Here we report that human cytomegalovirus (HCMV), a ubiquitous betaherpesvirus, alters the fate of internalized clathrin-independent endocytosis (CIE) cargo proteins, retaining them in virally reprogrammed SEs. We show that the small G protein ARF6 (ADP ribosylation factor 6), a regulator of CIE trafficking, is highly associated with SE membranes relative to uninfected cells. Combined with the observation of accumulated CIE cargo at the SE, these results suggest that infection diminishes the egress of ARF6 and its cargo from the SE. Expression of ubiquitin-specific protease 6 (USP6), also known as TRE17, was sufficient to restore ARF6 and some ARF6 cargo trafficking to the cell surface in infected cells. The USP activity of TRE17 was required to rescue both ARF6 and associated cargo from SE retention in infection. The finding that TRE17 expression does not rescue the trafficking of all CIE cargos retained at SEs in infection suggests that HCMV hijacks the normal sorting machinery and selectively sorts specific cargos into endocytic microdomains that are subject to alternative sorting fates. |
format | Online Article Text |
id | pubmed-6058287 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-60582872018-07-27 Virus Control of Trafficking from Sorting Endosomes Zeltzer, Sebastian Zeltzer, Carol A. Igarashi, Suzu Wilson, Jean Donaldson, Julie G. Goodrum, Felicia mBio Research Article The maintenance of cell surface proteins is critical to the ability of a cell to sense and respond to information in its environment. As such, modulation of cell surface composition and receptor trafficking is a potentially important target of control in virus infection. Sorting endosomes (SEs) are control stations regulating the recycling or degradation of internalized plasma membrane proteins. Here we report that human cytomegalovirus (HCMV), a ubiquitous betaherpesvirus, alters the fate of internalized clathrin-independent endocytosis (CIE) cargo proteins, retaining them in virally reprogrammed SEs. We show that the small G protein ARF6 (ADP ribosylation factor 6), a regulator of CIE trafficking, is highly associated with SE membranes relative to uninfected cells. Combined with the observation of accumulated CIE cargo at the SE, these results suggest that infection diminishes the egress of ARF6 and its cargo from the SE. Expression of ubiquitin-specific protease 6 (USP6), also known as TRE17, was sufficient to restore ARF6 and some ARF6 cargo trafficking to the cell surface in infected cells. The USP activity of TRE17 was required to rescue both ARF6 and associated cargo from SE retention in infection. The finding that TRE17 expression does not rescue the trafficking of all CIE cargos retained at SEs in infection suggests that HCMV hijacks the normal sorting machinery and selectively sorts specific cargos into endocytic microdomains that are subject to alternative sorting fates. American Society for Microbiology 2018-07-24 /pmc/articles/PMC6058287/ /pubmed/30042195 http://dx.doi.org/10.1128/mBio.00683-18 Text en Copyright © 2018 Zeltzer et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Zeltzer, Sebastian Zeltzer, Carol A. Igarashi, Suzu Wilson, Jean Donaldson, Julie G. Goodrum, Felicia Virus Control of Trafficking from Sorting Endosomes |
title | Virus Control of Trafficking from Sorting Endosomes |
title_full | Virus Control of Trafficking from Sorting Endosomes |
title_fullStr | Virus Control of Trafficking from Sorting Endosomes |
title_full_unstemmed | Virus Control of Trafficking from Sorting Endosomes |
title_short | Virus Control of Trafficking from Sorting Endosomes |
title_sort | virus control of trafficking from sorting endosomes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058287/ https://www.ncbi.nlm.nih.gov/pubmed/30042195 http://dx.doi.org/10.1128/mBio.00683-18 |
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