Endosomal compartment contributes to the propagation of CD95/Fas-mediated signals in type II cells

Paola Matarrese , Valeria Manganelli , Tina Garofalo , Antonella Tinari , Lucrezia Gambardella , Kenneth Ndebele , Roya Khosravi-Far , Maurizio Sorice , Mauro Degli Esposti , Walter Malorni (1)

1 Drug Research and Evaluation

Participation of diverse organelles to the intracellular signaling that follows CD95/Fas receptor ligation encompasses a series of subcellular changes that are mandatory for, or even bolster, the apoptotic cascade. In this work we analyzed the role of endocytosis in the propagation of cell death signaling 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-induced endocytosis also leads to an early and directional “movement” of endocytic vesicles towards mitochondrial compartment. In turn, this crosstalk between endosomal and mitochondrial compartments was followed by the loss of the mitochondrial membrane potential and apoptosis execution. This cell remodeling 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 multi-drug resistance (CEM VBL100). In these cells a reduced 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 signaling leading to type II cell demise.

Mots clés: Life Sciences

Paola Matarrese, Valeria Manganelli, Tina Garofalo, Antonella Tinari, Lucrezia Gambardella, et al.. Endosomal compartment contributes to the propagation of CD95/Fas-mediated signals in type II cells. Biochemical Journal, 2008, 413 (3), pp.467-478. ⟨10.1042/BJ20071704⟩. ⟨hal-00478940⟩