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Spatial differences in active caspase-8 defines its role in T-cell activation versus cell death.
- Source :
- Cell Death & Differentiation; Nov2008, Vol. 15 Issue 11, p1701-1711, 11p, 1 Color Photograph, 1 Black and White Photograph, 4 Diagrams, 1 Chart, 1 Graph
- Publication Year :
- 2008
-
Abstract
- Caspase-8, a cysteine-protease, initiates apoptosis when activated by death receptors. Caspase-8 is also essential for initiating T lymphocyte proliferation following T-cell antigen receptor (TCR) signaling. Given these disparate functions of caspase-8, we sought to determine whether this represented only a difference in the magnitude of caspase-8 activation, or different intracellular locations of active caspase-8. We demonstrate by high-resolution multicolor confocal laser scanning microscopy an aggregation of active caspase-8 within membrane lipid rafts in T cells stimulated with anti-CD3. This suggests that following TCR stimulation active caspase-8 physically interacts with lipid raft proteins, possibly to form a signaling platform. In contrast, Fas stimulation of T cells resulted in a much more profound activation of caspase-8 that was exclusively cytosolic. These confocal microscopic findings were confirmed using discontinuous sucrose gradient ultracentrifugation to isolate lipid raft versus cytosolic components. This sequestration model of caspase-8 activation was further supported by the observation that a classic caspase-8 substrate, BID, was not cleaved in CD3-stimulated T cells, but was cleaved after Fas engagement. Our data support a model that the location of active caspase-8 may profoundly influence its functional capacity as a regulator of either cell cycling or cell death.Cell Death and Differentiation (2008) 15, 1701–1711; doi:10.1038/cdd.2008.100; published online 11 July 2008 [ABSTRACT FROM AUTHOR]
- Subjects :
- ENZYMES
T cells
CELL death
APOPTOSIS
ANTIGENS
Subjects
Details
- Language :
- English
- ISSN :
- 13509047
- Volume :
- 15
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Cell Death & Differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 34715350
- Full Text :
- https://doi.org/10.1038/cdd.2008.100