We investigated the membrane localization of CD95 in type I and type II cells, which differ in their ability to recruit and activate caspase-8. We found that CD95 was preferentially located in lipid rafts of type I cells, while it was present both in raft and non-raft plasma membrane sub-domains of type II cells. After stimulation, CD95 located in phospholipid-rich plasma membrane was recruited to lipid rafts in both types of cells. Similarly, CD95 cross-linking resulted in caspase-independent translocation of FADD/MORT1 and caspase-8 to the lipid rafts, which was prevented by a death domain-defective receptor. CD95 internalization was then rapid in type I and delayed in type II cells and showed a substantial correlation with the kinetics of Fas-associated death domain (FADD) and caspase-8 recruitment to lipid rafts. Finally, electron microscopy analysis showed that after CD95 stimulation lipid rafts aggregated in large clusters that were internalized in endosomal vesicles, where caspase-8 underwent massive processing. Taken together, our data demonstrate that CD95 death-inducing signaling complex formation and internalization in type I and type II cells occur in lipid rafts, which are a major site of caspase-8 activation. © 2004 WILEY-VCH Verlag GmbH & Co. KGaA.
|Data di pubblicazione:||2004|
|Titolo:||CD95 DISC formation and internalizzation occur in lipid rafts of typeI and typeII cells|
|Autori:||ADRIANA ERAMO; MASSIMO SARGIACOMO; LUCIA RICCI VITIANI; MATILDE TODARO; STASSI G; CARLO GM MESSINA; ISABELLA PAROLINI; CESARE PESCHLE; RUGGERO DE MARIA|
|Tipologia:||Articolo su rivista|
|Citazione:||ADRIANA ERAMO, MASSIMO SARGIACOMO, LUCIA RICCI VITIANI, MATILDE TODARO, STASSI G, CARLO GM MESSINA, et al. (2004). CD95 DISC formation and internalizzation occur in lipid rafts of typeI and typeII cells. EUROPEAN JOURNAL OF IMMUNOLOGY, 34, 1930-1940.|
|Digital Object Identifier (DOI):||10.1002/eji.200324786|
|Appare nelle tipologie:||01 - Articolo su rivista|