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Dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids
Caveolae have long been implicated in endocytosis. Recent data question this link, and in the absence of specific cargoes the potential cellular function of caveolar endocytosis remains unclear. Here we develop new tools, including doubly genome-edited cell lines, to assay the subcellular dynamics o...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410672/ https://www.ncbi.nlm.nih.gov/pubmed/25897946 http://dx.doi.org/10.1038/ncomms7867 |
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author | Shvets, Elena Bitsikas, Vassilis Howard, Gillian Hansen, Carsten Gram Nichols, Benjamin J. |
author_facet | Shvets, Elena Bitsikas, Vassilis Howard, Gillian Hansen, Carsten Gram Nichols, Benjamin J. |
author_sort | Shvets, Elena |
collection | PubMed |
description | Caveolae have long been implicated in endocytosis. Recent data question this link, and in the absence of specific cargoes the potential cellular function of caveolar endocytosis remains unclear. Here we develop new tools, including doubly genome-edited cell lines, to assay the subcellular dynamics of caveolae using tagged proteins expressed at endogenous levels. We find that around 5% of the cellular pool of caveolae is present on dynamic endosomes, and is delivered to endosomes in a clathrin-independent manner. Furthermore, we show that caveolae are indeed likely to bud directly from the plasma membrane. Using a genetically encoded tag for electron microscopy and ratiometric light microscopy, we go on to show that bulk membrane proteins are depleted within caveolae. Although caveolae are likely to account for only a small proportion of total endocytosis, cells lacking caveolae show fundamentally altered patterns of membrane traffic when loaded with excess glycosphingolipid. Altogether, these observations support the hypothesis that caveolar endocytosis is specialized for transport of membrane lipid. |
format | Online Article Text |
id | pubmed-4410672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44106722015-05-08 Dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids Shvets, Elena Bitsikas, Vassilis Howard, Gillian Hansen, Carsten Gram Nichols, Benjamin J. Nat Commun Article Caveolae have long been implicated in endocytosis. Recent data question this link, and in the absence of specific cargoes the potential cellular function of caveolar endocytosis remains unclear. Here we develop new tools, including doubly genome-edited cell lines, to assay the subcellular dynamics of caveolae using tagged proteins expressed at endogenous levels. We find that around 5% of the cellular pool of caveolae is present on dynamic endosomes, and is delivered to endosomes in a clathrin-independent manner. Furthermore, we show that caveolae are indeed likely to bud directly from the plasma membrane. Using a genetically encoded tag for electron microscopy and ratiometric light microscopy, we go on to show that bulk membrane proteins are depleted within caveolae. Although caveolae are likely to account for only a small proportion of total endocytosis, cells lacking caveolae show fundamentally altered patterns of membrane traffic when loaded with excess glycosphingolipid. Altogether, these observations support the hypothesis that caveolar endocytosis is specialized for transport of membrane lipid. Nature Pub. Group 2015-04-21 /pmc/articles/PMC4410672/ /pubmed/25897946 http://dx.doi.org/10.1038/ncomms7867 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Shvets, Elena Bitsikas, Vassilis Howard, Gillian Hansen, Carsten Gram Nichols, Benjamin J. Dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids |
title | Dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids |
title_full | Dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids |
title_fullStr | Dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids |
title_full_unstemmed | Dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids |
title_short | Dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids |
title_sort | dynamic caveolae exclude bulk membrane proteins and are required for sorting of excess glycosphingolipids |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410672/ https://www.ncbi.nlm.nih.gov/pubmed/25897946 http://dx.doi.org/10.1038/ncomms7867 |
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