CD95 signaling via ceramide-rich membrane rafts
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
The Journal of Biological Chemistry
|March 30, 2001
Summary
Ceramide released by acid sphingomyelinase (ASM) is crucial for CD95 clustering and subsequent apoptosis. This ceramide-mediated clustering in membrane rafts is essential for CD95 signaling and cell death induction.
Area of Science:
- Cellular signaling
- Membrane biology
- Apoptosis
Background:
- Receptor clustering is a common mechanism in transmembrane signaling.
- The role of ceramide in CD95 receptor clustering and apoptosis is not fully understood.
Purpose of the Study:
- To investigate the role of acid sphingomyelinase (ASM)-released ceramide in CD95 clustering.
- To determine if ceramide is essential for CD95-mediated apoptosis.
Main Methods:
- In vitro and in vivo experiments.
- Assessing CD95 clustering in sphingolipid-rich membrane rafts.
- Evaluating apoptosis induction.
- Utilizing ASM-deficient cells and neutralizing surface ceramide.
Main Results:
- Extracellular ceramide, released by ASM translocation to the plasma membrane, enables CD95 clustering and apoptosis.
- ASM deficiency, raft disruption, or ceramide neutralization inhibits CD95 clustering and apoptosis.
- Natural ceramide can rescue ASM-deficient cells, restoring CD95 clustering and apoptosis.
Conclusions:
- CD95-mediated clustering by ceramide is a prerequisite for CD95 signaling and apoptosis.
- Ceramide plays a critical role in the initiation of CD95-induced cell death pathways.
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