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Inhibition of caveolar uptake, SV40 infection, and β1-integrin signaling by a nonnatural glycosphingolipid stereoisomer
Caveolar endocytosis is an important mechanism for the uptake of certain pathogens and toxins and also plays a role in the internalization of some plasma membrane (PM) lipids and proteins. However, the regulation of caveolar endocytosis is not well understood. We previously demonstrated that caveola...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064075/ https://www.ncbi.nlm.nih.gov/pubmed/17371832 http://dx.doi.org/10.1083/jcb.200609149 |
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author | Singh, Raman Deep Holicky, Eileen L. Cheng, Zhi-jie Kim, Seong-Youl Wheatley, Christine L. Marks, David L. Bittman, Robert Pagano, Richard E. |
author_facet | Singh, Raman Deep Holicky, Eileen L. Cheng, Zhi-jie Kim, Seong-Youl Wheatley, Christine L. Marks, David L. Bittman, Robert Pagano, Richard E. |
author_sort | Singh, Raman Deep |
collection | PubMed |
description | Caveolar endocytosis is an important mechanism for the uptake of certain pathogens and toxins and also plays a role in the internalization of some plasma membrane (PM) lipids and proteins. However, the regulation of caveolar endocytosis is not well understood. We previously demonstrated that caveolar endocytosis and β1-integrin signaling are stimulated by exogenous glycosphingolipids (GSLs). In this study, we show that a synthetic GSL with nonnatural stereochemistry, β-d-lactosyl-N-octanoyl-l-threo-sphingosine, (1) selectively inhibits caveolar endocytosis and SV40 virus infection, (2) blocks the clustering of lipids and proteins into GSLs and cholesterol-enriched microdomains (rafts) at the PM, and (3) inhibits β1-integrin activation and downstream signaling. Finally, we show that small interfering RNA knockdown of β1 integrin in human skin fibroblasts blocks caveolar endocytosis and the stimulation of signaling by a GSL with natural stereochemistry. These experiments identify a new compound that can interfere with biological processes by inhibiting microdomain formation and also identify β1 integrin as a potential mediator of signaling by GSLs. |
format | Text |
id | pubmed-2064075 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20640752007-11-29 Inhibition of caveolar uptake, SV40 infection, and β1-integrin signaling by a nonnatural glycosphingolipid stereoisomer Singh, Raman Deep Holicky, Eileen L. Cheng, Zhi-jie Kim, Seong-Youl Wheatley, Christine L. Marks, David L. Bittman, Robert Pagano, Richard E. J Cell Biol Research Articles Caveolar endocytosis is an important mechanism for the uptake of certain pathogens and toxins and also plays a role in the internalization of some plasma membrane (PM) lipids and proteins. However, the regulation of caveolar endocytosis is not well understood. We previously demonstrated that caveolar endocytosis and β1-integrin signaling are stimulated by exogenous glycosphingolipids (GSLs). In this study, we show that a synthetic GSL with nonnatural stereochemistry, β-d-lactosyl-N-octanoyl-l-threo-sphingosine, (1) selectively inhibits caveolar endocytosis and SV40 virus infection, (2) blocks the clustering of lipids and proteins into GSLs and cholesterol-enriched microdomains (rafts) at the PM, and (3) inhibits β1-integrin activation and downstream signaling. Finally, we show that small interfering RNA knockdown of β1 integrin in human skin fibroblasts blocks caveolar endocytosis and the stimulation of signaling by a GSL with natural stereochemistry. These experiments identify a new compound that can interfere with biological processes by inhibiting microdomain formation and also identify β1 integrin as a potential mediator of signaling by GSLs. The Rockefeller University Press 2007-03-26 /pmc/articles/PMC2064075/ /pubmed/17371832 http://dx.doi.org/10.1083/jcb.200609149 Text en Copyright © 2007, The Rockefeller University Press 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 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Singh, Raman Deep Holicky, Eileen L. Cheng, Zhi-jie Kim, Seong-Youl Wheatley, Christine L. Marks, David L. Bittman, Robert Pagano, Richard E. Inhibition of caveolar uptake, SV40 infection, and β1-integrin signaling by a nonnatural glycosphingolipid stereoisomer |
title | Inhibition of caveolar uptake, SV40 infection, and β1-integrin signaling by a nonnatural glycosphingolipid stereoisomer |
title_full | Inhibition of caveolar uptake, SV40 infection, and β1-integrin signaling by a nonnatural glycosphingolipid stereoisomer |
title_fullStr | Inhibition of caveolar uptake, SV40 infection, and β1-integrin signaling by a nonnatural glycosphingolipid stereoisomer |
title_full_unstemmed | Inhibition of caveolar uptake, SV40 infection, and β1-integrin signaling by a nonnatural glycosphingolipid stereoisomer |
title_short | Inhibition of caveolar uptake, SV40 infection, and β1-integrin signaling by a nonnatural glycosphingolipid stereoisomer |
title_sort | inhibition of caveolar uptake, sv40 infection, and β1-integrin signaling by a nonnatural glycosphingolipid stereoisomer |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064075/ https://www.ncbi.nlm.nih.gov/pubmed/17371832 http://dx.doi.org/10.1083/jcb.200609149 |
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