What question did this study set out to answer?

To elucidate the molecular mechanism by which acid sphingomyelinase and ceramide mediate CD95 receptor clustering and downstream apoptosis induction.

January 1, 2001Journal of Biological ChemistryOpen Access

CD95 Signaling via Ceramide-rich Membrane Rafts

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Authors

HGHeike GrassméUniversity of Duisburg-Essen AJAndreas JekleRapt Therapeutics (United States)ARAndrea RiehleUniversity of Duisburg-Essen

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Implication

Experimental study demonstrates that acid sphingomyelinase-released ceramide drives CD95 clustering and apoptosis in cells, indicating lipid rafts are necessary for death receptor signaling.

Key Points

To elucidate the molecular mechanism by which acid sphingomyelinase and ceramide mediate CD95 receptor clustering and downstream apoptosis induction.
Analyzed CD95 receptor translocation, clustering, and apoptosis signaling in vitro and in vivo.
Assessed cell responses under conditions of acid sphingomyelinase deficiency, membrane raft disruption, extracellular ceramide neutralization, and exogenous ceramide rescue.
CD95 stimulation triggered translocation of acid sphingomyelinase to the cell surface, generating extracellular ceramide that induced CD95 clustering in sphingolipid-rich membrane rafts and led to apoptosis.
Deficiency in acid sphingomyelinase, structural destruction of membrane rafts, or neutralization of surface ceramide completely prevented CD95 clustering and cell death, while natural ceramide rescued signaling exclusively in enzyme-deficient cells.

Cite This Study

Grassmé et al. (2001) studied this question.

synapsesocial.com/papers/6a783ae5e29fd788c9f7dffc https://doi.org/10.1074/jbc.m101207200

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Implication

Experimental study demonstrates that acid sphingomyelinase-released ceramide drives CD95 clustering and apoptosis in cells, indicating lipid rafts are necessary for death receptor signaling.

CD95 Signaling via Ceramide-rich Membrane Rafts

Discussion

Member takes

Implication

Key Points

Cite This Study

CD95 Signaling via Ceramide-rich Membrane Rafts

Discussion

Member takes

Implication

Key Points

Cite This Study

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