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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...

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Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
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.
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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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