Amplification of Fas-mediated apoptosis in type II cells via microdomain recruitment.
Fas triggers apoptosis via the caspase cascade when bound to its ligand FasL. In type I cells, Fas is concentrated into the plasma membrane lipid rafts, and these domains are required for the apoptotic signal to occur. In contrast, Fas is excluded from the microdomains in type II cells. We report that the coligation with Fas of the membrane receptor CD28 strongly increases Fas-induced apoptosis in type II T lymphocytes, whereas it has no effect in a type I cell line. The effect of CD28 is independent of its intracellular region and requires the recruitment of the microdomains. Indeed, upon CD28 costimulation, Fas is redistributed in the lipid rafts, and their disruption with a cholesterol chelator abrogates the effect of CD28. The microdomain-mediated cell death amplification does not alter death-induced signaling complex formation and is mediated by the enhancement of the mitochondrial apoptotic pathway. These findings indicate that the sensitivity to Fas-induced apoptosis of type II cells can be amplified in vivo by the recruitment of lipid rafts following interactions between nonapoptotic ligand/receptor pairs during cell-to-cell contacts.
Legembre
Patrick
P
Laboratoire CIRID, CNRS UMR 5164, Université de Bordeaux 2, 146 rue Léo Saignat, Bordeaux 33076, France.
Daburon
Sophie
S
Moreau
Patrick
P
Ichas
François
F
de Giorgi
Francesca
F
Moreau
Jean-François
JF
Taupin
Jean-Luc
JL
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D053222:Fas Ligand Protein; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism* / Q000502:physiology*
D018106:CD28 Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor