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Palmitoylation of human FasL modulates its cell death-inducing function
F Guardiola-Serrano1, A Rossin, N Cahuzac
1University of Nice-Sophia Antipolis, Centre National de la Recherche Scientifique, Equipe labelisée La Ligue, Institute of Developmental Biology and Cancer, UMR, Nice, France.
Cell Death & Disease
|March 4, 2011
Summary
Fas ligand (FasL) processing by ADAM10 counteracts cell death and is regulated by its membrane localization, interactions, and palmitoylation. This processing occurs in lipid rafts, requiring Fas receptor interaction for efficient killing.
Area of Science:
- Cell biology
- Immunology
- Molecular biology
Background:
- Fas ligand (FasL) is crucial for immune homeostasis and eliminating unwanted cells.
- FasL's potent cytotoxic activity necessitates strict regulation of its cell surface expression.
- ADAM10 and SPPL2a proteases process FasL, generating soluble forms and intracellular fragments.
Purpose of the Study:
- To investigate the regulation of FasL processing by ADAM10.
- To understand how FasL membrane localization, interactions, and modifications influence its processing and function.
- To elucidate the role of lipid rafts in FasL-mediated cell death.
Main Methods:
- Cell-based assays to study FasL processing.
- Analysis of FasL localization within membrane nanodomains (rafts).
- Investigation of FasL-Fas receptor interactions and palmitoylation.
Main Results:
- FasL processing by ADAM10 counteracts Fas-mediated cell death.
- FasL processing is regulated by its membrane localization, interactions, and palmitoylation.
- Processing preferentially occurs in cholesterol and sphingolipid-rich rafts, requiring Fas receptor interaction.
- FasL palmitoylation within its transmembrane domain is critical for killing and processing.
Conclusions:
- ADAM10-mediated FasL processing is a regulatory mechanism that can counteract Fas-mediated cell death.
- Lipid raft localization and Fas receptor engagement are essential for efficient FasL processing and cytotoxic activity.
- FasL palmitoylation is a key modification for both its processing and its ability to induce cell death.
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