The death-inducing signalling complex is recruited to lipid rafts in Fas-induced apoptosis

Scheel‐Toellner, Dagmar; Wang, K; Singh, R. P.; Majeed, Shahid; Raza, Karim; Curnow, S. John; Salmon, M; Lord, Janet M.

doi:10.1016/s0006-291x(02)02311-2

Cited by 123 publications

(108 citation statements)

References 18 publications

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…In agreement with this result, recent reports also documented the constitutive presence of a portion of Fas in lipid rafts in thymocytes and the L12.10-Fas T-cell line. [28][29][30] In contrast to our results (Figures 5-8) and those of Algeciras-Schimnich et al, 31 it has been reported that caspase-8 30 or both FADD and caspase-8 are recruited to lipid rafts upon Fas stimulation. 28,29 We believe that our mAbs are specific and sensitive enough to detect endogenous FADD and caspase-8 (Figures 1, 2).…”

Section: Fadd and Caspase-8 Do Not Localise In Membrane Raftscontrasting

confidence: 99%

“…[24][25][26] These studies should, however, be viewed with caution as the amount of TCR/CD3 and their signal transducers recovered with rafts depends on the type of detergent used. 27 Recently, it was suggested that activation of Fas leads to the recruitment of FADD and caspase-8 into lipid rafts in mouse thymocytes, 28 human CD4 þ T cells 29 and in a human lymphoblastoid cell line, 30 indicating that such intracellular trafficking might also play a role in 'death receptor'-induced apoptosis. However, not all investigators have been able to reproduce these findings.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Modifications and intracellular trafficking of FADD/MORT1 and caspase-8 after stimulation of T lymphocytes

et al. 2004

View full text Add to dashboard Cite

The adaptor protein FADD/MORT1 is essential for apoptosis induced by 'death receptors', such as Fas (APO-1/CD95), mediating aggregation and autocatalytic activation of caspase-8. Perhaps surprisingly, FADD and caspase-8 are also critical for mitogen-induced proliferation of T lymphocytes. We generated novel monoclonal antibodies specific for mouse FADD and caspase-8 to investigate whether cellular responses, apoptosis or proliferation, might be explained by differences in post-translational modification and subcellular localisation of these proteins. During both apoptosis signalling and mitogenic activation, FADD and caspase-8 aggregated in multiprotein complexes and formed caps at the plasma membrane but they did not colocalise with lipid rafts. Interestingly, mitogenic stimulation, but not Fas ligation, induced a unique post-translational modification of FADD. These different modifications may determine whether FADD and caspase-8 induce cell death or proliferation.

show abstract

Section: Fadd and Caspase-8 Do Not Localise In Membrane Raftscontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modifications and intracellular trafficking of FADD/MORT1 and caspase-8 after stimulation of T lymphocytes

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Most of these studies suggested that the formation of ceramide-enriched membrane platforms is initiated within small cholesterol-and sphingolipid-enriched membrane rafts. The notion that rafts are important for the induction of apoptosis is supported by several recent studies demonstrating that destruction of these membrane rafts prevents CD95 clustering, recruitment of FADD and caspase 8 and apoptosis by CD95 (Cremesti et al, 2001;Grassme et al, 2001b;Hueber et al, 2002;Scheel-Toellner et al, 2002). However, our studies go far beyond the finding that rafts are involved in apoptosis and suggest a mechanism how small rafts in resting cells can be transformed into a signaling unit that transmits signals from out to inside of the cell.…”

Section: Discussionsupporting

confidence: 72%

“…Rafts are organized membrane domains mainly composed of glycosphingolipids, sphingomyelin, cholesterol and specific membrane proteins (Simons and Ikonen, 1997;Brown and London, 1998). Several studies indicated that rafts are required to cluster CD95 and to recruit FADD, caspase 8 and 3 to CD95 upon stimulation (Grassme et al, 2001bHueber et al, 2002;Scheel-Toellner et al, 2002;Delmas et al, 2003;Aouad et al, 2004;Eramo et al, 2004). Accordingly, disruption of rafts prevented CD95-induced apoptosis, at least in most cells (Grassme et al, 2001b;Cremesti et al, 2001;Hueber et al, 2002;Scheel-Toellner et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

TRAIL activates acid sphingomyelinase via a redox mechanism and releases ceramide to trigger apoptosis

2006

View full text Add to dashboard Cite

We have previously shown that activation of the acid sphingomyelinase (ASM), the release of ceramide and the formation of ceramide-enriched membrane domains are central for the induction of apoptosis by CD95. Here, we demonstrate that tumor necrosis factor-related apoptosisinducing ligand (TRAIL) and CD95 activate the ASM via a redox mechanism resulting in release of ceramide and formation of ceramide-enriched membrane platforms. Ceramide-enriched membrane platforms serve to cluster DR5 upon stimulation. Antioxidants prevent TRAILmediated stimulation of ASM, the release of ceramide, the formation of ceramide-enriched membrane platforms and the induction of apoptosis by TRAIL. Further, ASMdeficient splenocytes fail to cluster DR5 in ceramideenriched membrane domains upon TRAIL stimulation and resist TRAIL-induced apoptosis, events that were restored by addition of natural C 16 -ceramide. A dose-response analysis indicates that ceramide-enriched membrane platforms greatly sensitized tumor cells to TRAIL-induced apoptosis. Our data indicate that ceramide-enriched membrane platforms are required for the signaling of TRAIL-DR5 complexes under physiological conditions.

show abstract

“…27,28 To understand the relevance of this reaction for CD44 and Fas colocalization during apoptosis induction in vitro, we performed functional assays using the Jurkat CD44s and CD44v2-10 transfected cells. Both transfectants were treated with methyl-beta cyclodextrin (MbCD), followed by treatment with FasL.…”

Section: Colocalization Of Cd44v and Fasmentioning

confidence: 99%

A novel antiapoptotic mechanism based on interference of Fas signaling by CD44 variant isoforms

et al. 2005

View full text Add to dashboard Cite

There is growing evidence that one of the central common characteristics of tumor and inflammatory cells is their resistance to programmed cell death. This feature results in the accumulation of harmful cells, which are mostly refractory to Fas (FAS, APO-1)-mediated apoptosis. A molecule found on these cells is the transmembrane receptor CD44 with its variant isoforms (CD44v). The establishment of transfectants expressing different CD44v isoforms allowed us to demonstrate that the CD44v6 and CD44v9 isoforms exhibit an antiapoptotic effect and can block Fas-mediated apoptosis. Moreover, we observed that CD44v6 and CD44v9 colocalize and interact with Fas. Importantly, an anti-CD44v6 antibody can abolish the antiapoptotic effect of CD44v6. These results are the first to show that CD44v isoforms interfere with Fas signaling. Our findings improve the understanding of the pathogenesis of cancer and autoimmunity and open new strategies to treat such disorders.

show abstract

The death-inducing signalling complex is recruited to lipid rafts in Fas-induced apoptosis

Cited by 123 publications

References 18 publications

Modifications and intracellular trafficking of FADD/MORT1 and caspase-8 after stimulation of T lymphocytes

Modifications and intracellular trafficking of FADD/MORT1 and caspase-8 after stimulation of T lymphocytes

TRAIL activates acid sphingomyelinase via a redox mechanism and releases ceramide to trigger apoptosis

A novel antiapoptotic mechanism based on interference of Fas signaling by CD44 variant isoforms

Contact Info

Product

Resources

About