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Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease
Gaucher disease is a lysosomal storage disease characterized by the malfunction of glucocerebrosidase resulting in the accumulation of glucosylceramide and other sphingolipids in certain cells. Although the disease symptoms are usually attributed to the storage of undigested substrate in lysosomes,...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760709/ https://www.ncbi.nlm.nih.gov/pubmed/29317695 http://dx.doi.org/10.1038/s41598-017-18405-8 |
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author | Batta, Gyula Soltész, Lilla Kovács, Tamás Bozó, Tamás Mészár, Zoltán Kellermayer, Miklós Szöllősi, János Nagy, Peter |
author_facet | Batta, Gyula Soltész, Lilla Kovács, Tamás Bozó, Tamás Mészár, Zoltán Kellermayer, Miklós Szöllősi, János Nagy, Peter |
author_sort | Batta, Gyula |
collection | PubMed |
description | Gaucher disease is a lysosomal storage disease characterized by the malfunction of glucocerebrosidase resulting in the accumulation of glucosylceramide and other sphingolipids in certain cells. Although the disease symptoms are usually attributed to the storage of undigested substrate in lysosomes, here we show that glycosphingolipids accumulating in the plasma membrane cause profound changes in the properties of the membrane. The fluidity of the sphingolipid-enriched membrane decreased accompanied by the enlargement of raft-like ordered membrane domains. The mobility of non-raft proteins and lipids was severely restricted, while raft-resident components were only mildly affected. The rate of endocytosis of transferrin receptor, a non-raft protein, was significantly retarded in Gaucher cells, while the endocytosis of the raft-associated GM1 ganglioside was unaffected. Interferon-γ-induced STAT1 phosphorylation was also significantly inhibited in Gaucher cells. Atomic force microscopy revealed that sphingolipid accumulation was associated with a more compliant membrane capable of producing an increased number of nanotubes. The results imply that glycosphingolipid accumulation in the plasma membrane has significant effects on membrane properties, which may be important in the pathogenesis of Gaucher disease. |
format | Online Article Text |
id | pubmed-5760709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57607092018-01-17 Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease Batta, Gyula Soltész, Lilla Kovács, Tamás Bozó, Tamás Mészár, Zoltán Kellermayer, Miklós Szöllősi, János Nagy, Peter Sci Rep Article Gaucher disease is a lysosomal storage disease characterized by the malfunction of glucocerebrosidase resulting in the accumulation of glucosylceramide and other sphingolipids in certain cells. Although the disease symptoms are usually attributed to the storage of undigested substrate in lysosomes, here we show that glycosphingolipids accumulating in the plasma membrane cause profound changes in the properties of the membrane. The fluidity of the sphingolipid-enriched membrane decreased accompanied by the enlargement of raft-like ordered membrane domains. The mobility of non-raft proteins and lipids was severely restricted, while raft-resident components were only mildly affected. The rate of endocytosis of transferrin receptor, a non-raft protein, was significantly retarded in Gaucher cells, while the endocytosis of the raft-associated GM1 ganglioside was unaffected. Interferon-γ-induced STAT1 phosphorylation was also significantly inhibited in Gaucher cells. Atomic force microscopy revealed that sphingolipid accumulation was associated with a more compliant membrane capable of producing an increased number of nanotubes. The results imply that glycosphingolipid accumulation in the plasma membrane has significant effects on membrane properties, which may be important in the pathogenesis of Gaucher disease. Nature Publishing Group UK 2018-01-09 /pmc/articles/PMC5760709/ /pubmed/29317695 http://dx.doi.org/10.1038/s41598-017-18405-8 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Batta, Gyula Soltész, Lilla Kovács, Tamás Bozó, Tamás Mészár, Zoltán Kellermayer, Miklós Szöllősi, János Nagy, Peter Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease |
title | Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease |
title_full | Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease |
title_fullStr | Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease |
title_full_unstemmed | Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease |
title_short | Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease |
title_sort | alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of gaucher disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760709/ https://www.ncbi.nlm.nih.gov/pubmed/29317695 http://dx.doi.org/10.1038/s41598-017-18405-8 |
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