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Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis
Engagement of the Fas receptor (CD95) initiates multiple signaling pathways that lead to apoptosis, such as the formation of death-inducing signaling complex (DISC), activation of caspase cascades, and the generation of the lipid messenger, ceramide. Sphingomyelin (SM) is a major component of lipid...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213006/ https://www.ncbi.nlm.nih.gov/pubmed/16009715 http://dx.doi.org/10.1084/jem.20041685 |
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author | Miyaji, Michihiko Jin, Zhe-Xiong Yamaoka, Shohei Amakawa, Ryuichi Fukuhara, Shirou Sato, Satoshi B. Kobayashi, Toshihide Domae, Naochika Mimori, Tsuneyo Bloom, Eda T. Okazaki, Toshiro Umehara, Hisanori |
author_facet | Miyaji, Michihiko Jin, Zhe-Xiong Yamaoka, Shohei Amakawa, Ryuichi Fukuhara, Shirou Sato, Satoshi B. Kobayashi, Toshihide Domae, Naochika Mimori, Tsuneyo Bloom, Eda T. Okazaki, Toshiro Umehara, Hisanori |
author_sort | Miyaji, Michihiko |
collection | PubMed |
description | Engagement of the Fas receptor (CD95) initiates multiple signaling pathways that lead to apoptosis, such as the formation of death-inducing signaling complex (DISC), activation of caspase cascades, and the generation of the lipid messenger, ceramide. Sphingomyelin (SM) is a major component of lipid rafts, which are specialized structures that enhance the efficiency of membrane receptor signaling and are a main source of ceramide. However, the functions of SM in Fas-mediated apoptosis have yet to be clearly defined, as the responsible genes have not been identified. After cloning a gene responsible for SM synthesis, SMS1, we established SM synthase–defective WR19L cells transfected with the human Fas gene (WR/Fas-SM(−)), and cells that have been functionally restored by transfection with SMS1 (WR/Fas-SMS1). We show that expression of membrane SM enhances Fas-mediated apoptosis through increasing DISC formation, activation of caspases, efficient translocation of Fas into lipid rafts, and subsequent Fas clustering. Furthermore, WR/Fas-SMS1 cells, but not WR/Fas-SM(−) cells, showed a considerable increase in ceramide generation within lipid rafts upon Fas stimulation. These data suggest that a membrane SM is important for Fas clustering through aggregation of lipid rafts, leading to Fas-mediated apoptosis. |
format | Text |
id | pubmed-2213006 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22130062008-03-11 Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis Miyaji, Michihiko Jin, Zhe-Xiong Yamaoka, Shohei Amakawa, Ryuichi Fukuhara, Shirou Sato, Satoshi B. Kobayashi, Toshihide Domae, Naochika Mimori, Tsuneyo Bloom, Eda T. Okazaki, Toshiro Umehara, Hisanori J Exp Med Article Engagement of the Fas receptor (CD95) initiates multiple signaling pathways that lead to apoptosis, such as the formation of death-inducing signaling complex (DISC), activation of caspase cascades, and the generation of the lipid messenger, ceramide. Sphingomyelin (SM) is a major component of lipid rafts, which are specialized structures that enhance the efficiency of membrane receptor signaling and are a main source of ceramide. However, the functions of SM in Fas-mediated apoptosis have yet to be clearly defined, as the responsible genes have not been identified. After cloning a gene responsible for SM synthesis, SMS1, we established SM synthase–defective WR19L cells transfected with the human Fas gene (WR/Fas-SM(−)), and cells that have been functionally restored by transfection with SMS1 (WR/Fas-SMS1). We show that expression of membrane SM enhances Fas-mediated apoptosis through increasing DISC formation, activation of caspases, efficient translocation of Fas into lipid rafts, and subsequent Fas clustering. Furthermore, WR/Fas-SMS1 cells, but not WR/Fas-SM(−) cells, showed a considerable increase in ceramide generation within lipid rafts upon Fas stimulation. These data suggest that a membrane SM is important for Fas clustering through aggregation of lipid rafts, leading to Fas-mediated apoptosis. The Rockefeller University Press 2005-07-18 /pmc/articles/PMC2213006/ /pubmed/16009715 http://dx.doi.org/10.1084/jem.20041685 Text en Copyright © 2005, 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 | Article Miyaji, Michihiko Jin, Zhe-Xiong Yamaoka, Shohei Amakawa, Ryuichi Fukuhara, Shirou Sato, Satoshi B. Kobayashi, Toshihide Domae, Naochika Mimori, Tsuneyo Bloom, Eda T. Okazaki, Toshiro Umehara, Hisanori Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis |
title | Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis |
title_full | Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis |
title_fullStr | Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis |
title_full_unstemmed | Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis |
title_short | Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis |
title_sort | role of membrane sphingomyelin and ceramide in platform formation for fas-mediated apoptosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213006/ https://www.ncbi.nlm.nih.gov/pubmed/16009715 http://dx.doi.org/10.1084/jem.20041685 |
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