Document Detail

Endosomal compartment contributes to the propagation of CD95/Fas-mediated signals in type II cells.
MedLine Citation:
PMID:  18442358     Owner:  NLM     Status:  MEDLINE    
Participation of diverse organelles in the intracellular signalling that follows CD95/Fas receptor ligation encompasses a series of subcellular changes that are mandatory for, or even bolster, the apoptotic cascade. In the present study, we analysed the role of endocytosis in the propagation of cell death signalling after CD95/Fas engagement in type II cells (CEM cells). We show that this receptor-ligand interaction triggers endocytosis independently of any caspase activation. This FasL (Fas ligand)-induced endocytosis also leads to an early and directional 'movement' of endocytic vesicles towards the mitochondrial compartment. In turn, this cross-talk between endosomal and mitochondrial compartments was followed by the loss of the mitochondrial membrane potential and apoptosis execution. This cell remodelling was absent in receptor-independent cell death, such as that induced by the mitochondriotropic drug staurosporine, and in a CEM cell line selected for its multidrug resistance (CEM VBL100). In these cells a reduced FasL (Fas ligand)-induced endocytosis and a reduced organelle cross-talk corresponded to a reduced apoptosis. Altogether, these findings suggest a key role of endocytosis in the propagation and amplification of the CD95/Fas-activated signalling leading to type II cell demise.
Paola Matarrese; Valeria Manganelli; Tina Garofalo; Antonella Tinari; Lucrezia Gambardella; Kenneth Ndebele; Roya Khosravi-Far; Maurizio Sorice; Mauro Degli Esposti; Walter Malorni
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  413     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-10     Completed Date:  2008-09-08     Revised Date:  2013-03-27    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  467-78     Citation Subset:  IM    
Department of Drug Research and Evaluation, Section of Cell Aging and Degeneration, Istituto Superiore di Sanità, viale Regina Elena 299, 00161 Rome, Italy.
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MeSH Terms
Antigens, CD95 / metabolism*
Apoptosis / drug effects,  physiology*
Cell Line
Endocytosis / drug effects,  physiology*
Fas Ligand Protein / pharmacology
Fluorescent Antibody Technique
Matrix Metalloproteinases / metabolism
Membrane Potential, Mitochondrial / drug effects
Microscopy, Electron, Transmission
Monensin / pharmacology
Staurosporine / pharmacology
Grant Support
BB/C508469//Biotechnology and Biological Sciences Research Council; BB/C508469/1//Biotechnology and Biological Sciences Research Council; HL0808192/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Antigens, CD95; 0/Fas Ligand Protein; 17090-79-8/Monensin; 62996-74-1/Staurosporine; EC 3.4.24.-/Matrix Metalloproteinases
Comment In:
Biochem J. 2008 Aug 1;413(3):e11-2   [PMID:  18613813 ]

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