Ceramide enables fas to cap and kill - PubMed (original) (raw)
. 2001 Jun 29;276(26):23954-61.
doi: 10.1074/jbc.M101866200. Epub 2001 Apr 3.
Affiliations
- PMID: 11287428
- DOI: 10.1074/jbc.M101866200
Free article
Ceramide enables fas to cap and kill
A Cremesti et al. J Biol Chem. 2001.
Free article
Abstract
Recent studies suggest that trimerization of Fas is insufficient for apoptosis induction and indicate that super-aggregation of trimerized Fas might be prerequisite. For many cell surface receptors, cross-linking by multivalent ligands or antibodies induces their lateral segregation within the plasma membrane and co-localization into "caps" on one pole of the cell. In this study, we show that capping of Fas is essential for optimal function and that capping is ceramide-dependent. In Jurkat T lymphocytes and in primary cultures of hepatocytes, ceramide elevation was detected as early as 15-30 s and peaked at 1 min after CH-11 and Jo2 anti-Fas antibody treatment, respectively. Capping was detected 30 s after Fas ligation, peaked at 2 min, and was maintained at a lower level for as long as 30 min in both cell types. Ceramide generation appeared essential for capping. Acid sphingomyelinase -/- hepatocytes were defective in Jo2-induced ceramide generation, capping, and apoptosis, and nanomolar concentrations of C(16)-ceramide restored these events. To further explore the role of ceramide in capping of Fas, we employed FLAG-tagged soluble Fas ligand (sFasL), which binds trimerized Fas but is unable to induce capping or apoptosis in Jurkat cells. Cross-linking of sFasL with M2 anti-FLAG antibody induced both events. Pretreatment of cells with natural C(16)-ceramide bypassed the necessity for forced antibody cross-linking and enabled sFasL to cap and kill. The presence of intact sphingolipid-enriched membrane domains may be essential for Fas capping since their disruption with cholesterol-depleting agents abrogated capping and prevented apoptosis. These data suggest that capping is a ceramide-dependent event required for optimal Fas signaling in some cells.
Similar articles
- Natural ceramide reverses Fas resistance of acid sphingomyelinase(-/-) hepatocytes.
Paris F, Grassmé H, Cremesti A, Zager J, Fong Y, Haimovitz-Friedman A, Fuks Z, Gulbins E, Kolesnick R. Paris F, et al. J Biol Chem. 2001 Mar 16;276(11):8297-305. doi: 10.1074/jbc.M008732200. Epub 2000 Nov 28. J Biol Chem. 2001. PMID: 11096096 - Increase of nuclear ceramide through caspase-3-dependent regulation of the "sphingomyelin cycle" in Fas-induced apoptosis.
Watanabe M, Kitano T, Kondo T, Yabu T, Taguchi Y, Tashima M, Umehara H, Domae N, Uchiyama T, Okazaki T. Watanabe M, et al. Cancer Res. 2004 Feb 1;64(3):1000-7. doi: 10.1158/0008-5472.can-03-1383. Cancer Res. 2004. PMID: 14871831 - Role of acidic sphingomyelinase in Fas/CD95-mediated cell death.
Lin T, Genestier L, Pinkoski MJ, Castro A, Nicholas S, Mogil R, Paris F, Fuks Z, Schuchman EH, Kolesnick RN, Green DR. Lin T, et al. J Biol Chem. 2000 Mar 24;275(12):8657-63. doi: 10.1074/jbc.275.12.8657. J Biol Chem. 2000. PMID: 10722706 - Ceramide and cell death receptor clustering.
Gulbins E, Grassmé H. Gulbins E, et al. Biochim Biophys Acta. 2002 Dec 30;1585(2-3):139-45. doi: 10.1016/s1388-1981(02)00334-7. Biochim Biophys Acta. 2002. PMID: 12531547 Review. - The role of ceramide in the cellular response to cytotoxic agents.
Jarvis WD, Grant S. Jarvis WD, et al. Curr Opin Oncol. 1998 Nov;10(6):552-9. doi: 10.1097/00001622-199811000-00013. Curr Opin Oncol. 1998. PMID: 9818235 Review.
Cited by
- Diabetic retinopathy is a ceramidopathy reversible by anti-ceramide immunotherapy.
Dorweiler TF, Singh A, Ganju A, Lydic TA, Glazer LC, Kolesnick RN, Busik JV. Dorweiler TF, et al. Cell Metab. 2024 Jul 2;36(7):1521-1533.e5. doi: 10.1016/j.cmet.2024.04.013. Epub 2024 May 7. Cell Metab. 2024. PMID: 38718792 - A Novel Non-Psychoactive Fatty Acid from a Marine Snail, Conus inscriptus, Signals Cannabinoid Receptor 1 (CB1) to Accumulate Apoptotic C16:0 and C18:0 Ceramides in Teratocarcinoma Cell Line PA1.
Vijayaraghavan CS, Raman LS, Surenderan S, Kaur H, Chinambedu MD, Thyagarajan SP, Gnanambal Krishnan ME. Vijayaraghavan CS, et al. Molecules. 2024 Apr 11;29(8):1737. doi: 10.3390/molecules29081737. Molecules. 2024. PMID: 38675558 Free PMC article. - Serotonin Signaling through Lipid Membranes.
Kalinichenko LS, Kornhuber J, Sinning S, Haase J, Müller CP. Kalinichenko LS, et al. ACS Chem Neurosci. 2024 Apr 3;15(7):1298-1320. doi: 10.1021/acschemneuro.3c00823. Epub 2024 Mar 18. ACS Chem Neurosci. 2024. PMID: 38499042 Free PMC article. Review. - Ceramide as an endothelial cell surface receptor and a lung-specific lipid vascular target for circulating ligands.
Staquicini DI, Cardó-Vila M, Rotolo JA, Staquicini FI, Tang FHF, Smith TL, Ganju A, Schiavone C, Dogra P, Wang Z, Cristini V, Giordano RJ, Ozawa MG, Driessen WHP, Proneth B, Souza GR, Brinker LM, Noureddine A, Snider AJ, Canals D, Gelovani JG, Petrache I, Tuder RM, Obeid LM, Hannun YA, Kolesnick RN, Brinker CJ, Pasqualini R, Arap W. Staquicini DI, et al. Proc Natl Acad Sci U S A. 2023 Aug 22;120(34):e2220269120. doi: 10.1073/pnas.2220269120. Epub 2023 Aug 14. Proc Natl Acad Sci U S A. 2023. PMID: 37579172 Free PMC article. - The link between the sphingolipid rheostat and obstructive sleep apnea.
Horváth P, Büdi L, Hammer D, Varga R, Losonczy G, Tárnoki ÁD, Tárnoki DL, Mészáros M, Bikov A. Horváth P, et al. Sci Rep. 2023 May 11;13(1):7675. doi: 10.1038/s41598-023-34717-4. Sci Rep. 2023. PMID: 37169814 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous