Whereas ligation of the CD95 death receptor in the plasma membrane of so-called type I cells leads to a direct caspase 8-dependent activation of downstream effector caspases, mitochondrial amplification of caspase 8-derived signals is required in so-called type II cells in order to execute apoptotic cell death. In type I cells CD95L (CD95 ligand) binding to CD95 results in a ceramide-dependent formation of the DISC (death-inducing signalling complex) and caspase 8-dependent CD95 clustering in the plasma membrane, followed by an internalization of these multimeric-receptor–DISC complexes. In contrast, in the hepatocyte, a type II cell, the bulk of CD95 is stored intracellularly under resting conditions and only a few ‘sentinel’ CD95 receptors are present in the plasma membrane. However, their activation by CD95L is sufficient to trigger a caspase 8-dependent endosomal acidification and a ceramide-dependent trafficking of intracellularly stored CD95 to the plasma membrane, thereby amplifying CD95 activation. Thus, in both type I and type II cells, ceramide and CD95 receptor endo- and exo-cytosis are involved in CD95-mediated apoptosis, but apparently in different ways. This, however, is not the only effect of CD95 ligation on intracellular membrane flow in type II cells, and evidence has been presented that soon after CD95 ligation Golgi elements intermix caspase-dependently with mitochondria. In this issue of the Biochemical Journal, Matarrese et al. report another aspect on endocytosis in response to CD95 ligation in type II cells, namely a caspase-independent endocytosis with vesicle translocation to the mitochondrial compartment, suggestive of an interplay between both organelles in the sense of an ‘organelle scrambling’. Thus early effects of CD95 activation on intracellular membrane flow may be much more complex than previously thought, but much has still to be learned about signalling mechanisms and the role they play in apoptosis.
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August 2008
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Commentary|
July 15 2008
CD95 ligation and intracellular membrane flow
Roland Reinehr;
Roland Reinehr
1Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
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Dieter Häussinger
Dieter Häussinger
1
1Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
1To whom correspondence should be addressed (email haeussin@uni-duesseldorf.de).
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Publisher: Portland Press Ltd
Received:
May 29 2008
Revision Received:
June 03 2008
Accepted:
June 04 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 413 (3): e11–e12.
Article history
Received:
May 29 2008
Revision Received:
June 03 2008
Accepted:
June 04 2008
Connected Content
A commentary has been published:
Endosomal compartment contributes to the propagation of CD95/Fas-mediated signals in type II cells
Citation
Roland Reinehr, Dieter Häussinger; CD95 ligation and intracellular membrane flow. Biochem J 1 August 2008; 413 (3): e11–e12. doi: https://doi.org/10.1042/BJ20081094
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