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.
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Research Article|
July 15 2008
Endosomal compartment contributes to the propagation of CD95/Fas-mediated signals in type II cells
Paola Matarrese;
Paola Matarrese
1
*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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Valeria Manganelli;
Valeria Manganelli
1
†Department of Experimental Medicine, Università ‘La Sapienza’, Rome, Italy
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Tina Garofalo;
Tina Garofalo
†Department of Experimental Medicine, Università ‘La Sapienza’, Rome, Italy
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Antonella Tinari;
Antonella Tinari
‡Technology and Health, Istituto Superiore di Sanità, Rome, Italy
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Lucrezia Gambardella;
Lucrezia Gambardella
*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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Kenneth Ndebele;
Kenneth Ndebele
§Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, U.S.A.
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Roya Khosravi-Far;
Roya Khosravi-Far
§Department of Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, U.S.A.
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Maurizio Sorice;
Maurizio Sorice
†Department of Experimental Medicine, Università ‘La Sapienza’, Rome, Italy
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Mauro Degli Esposti;
Mauro Degli Esposti
2
∥Faculty of Life Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, U.K.
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Walter Malorni
*Department of Drug Research and Evaluation, Section of Cell Aging and Degeneration, Istituto Superiore di Sanità, viale Regina Elena 299, 00161 Rome, Italy
3To whom correspondence should be addressed (email malorni@iss.it).
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Publisher: Portland Press Ltd
Received:
December 19 2007
Revision Received:
April 16 2008
Accepted:
April 28 2008
Accepted Manuscript online:
April 28 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 413 (3): 467–478.
Article history
Received:
December 19 2007
Revision Received:
April 16 2008
Accepted:
April 28 2008
Accepted Manuscript online:
April 28 2008
Connected Content
This is a commentary on:
CD95 ligation and intracellular membrane flow
Citation
Paola Matarrese, Valeria Manganelli, Tina Garofalo, Antonella Tinari, Lucrezia Gambardella, Kenneth Ndebele, Roya Khosravi-Far, Maurizio Sorice, Mauro Degli Esposti, Walter Malorni; Endosomal compartment contributes to the propagation of CD95/Fas-mediated signals in type II cells. Biochem J 1 August 2008; 413 (3): 467–478. doi: https://doi.org/10.1042/BJ20071704
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