A novel role of microtubular cytoskeleton in the dynamics of caspase-dependent Fas/CD95 death receptor complexes during apoptosis.
The activation of cysteine-aspartic proteases or caspases and the dynamic arrangement of cytoskeletal components are crucial during apoptosis. Here we describe the fate of Fas downstream of the FasL-induced internalization step, including formation of caspase-dependent SDS-stable Fas complexes, which is mediated by cytoskeleton integrity. We show, in particular, that following FasL treatment, the Fas lower aggregate complex can be co-immunoprecipitated with tubulin and an active form of caspase-8 and that this interaction contributes to the propagation of FasL-induced cell death. The importance of cytoskeletal components during FasL-induced apoptosis is highlighted by our detection of a pool of microtubule-associated Fas complexes.
Equipe labelisée La Ligue; Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Nice, France.
Eszter
E
Doma
Krittalak
K
Chakrabandhu
Anne-Odile
AO
Hueber
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D053222:Fas Ligand Protein / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008870:Microtubules / Q000378:metabolism / Q000502:physiology*; D019014:fas Receptor / Q000378:metabolism*
D053222:Fas Ligand Protein; D019014:fas Receptor; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases