2005年7月
Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis
JOURNAL OF EXPERIMENTAL MEDICINE
- 巻
- 202
- 号
- 2
- 開始ページ
- 249
- 終了ページ
- 259
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1084/jem.20041685
- 出版者・発行元
- ROCKEFELLER UNIV PRESS
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.
- リンク情報
- ID情報
-
- DOI : 10.1084/jem.20041685
- ISSN : 0022-1007
- PubMed ID : 16009715
- Web of Science ID : WOS:000230597800008