CD95 death-inducing signaling complex formation and internalization occur in lipid rafts of type I and type II cells

Ruggero De Maria Marchiano, Giovanni Sette, Adriana Eramo, Massimo Sargiacomo, Lucia Ricci-Vitiani, Matilde Todaro, Giorgio Stassi, Carlo G.M. Messina, Isabella Parolini, Fiorenza Lotti, Cesare Peschle

Risultato della ricerca: Contributo in rivistaArticolo in rivista

91 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)1930-1940
Numero di pagine11
RivistaEuropean Journal of Immunology
Volume34
DOI
Stato di pubblicazionePubblicato - 2004

Keywords

  • Apoptosis
  • CD95
  • Caspase-8
  • Caspases
  • Cell Line, Tumor
  • Cholesterol
  • Death Domain Receptor Signaling Adaptor Proteins
  • Endocytosis
  • Humans
  • Immunology
  • Immunology and Allergy
  • Lipid rafts
  • Membrane Microdomains
  • Protein Binding
  • Protein Transport
  • Receptors, Tumor Necrosis Factor
  • Signal Transduction
  • T-Lymphocytes
  • fas Receptor

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