期刊
CELL DEATH AND DIFFERENTIATION
卷 20, 期 4, 页码 599-610出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2012.156
关键词
apoptosis; live-cell imaging; quantitative biology; caspase sensor
资金
- Initiative and Networking Fund of the Helmholtz Association within the Helmholtz Alliance on Systems Biology/ SBCancer
- BMBF
- Center for Modeling and Simulation in the Biosciences (BIOMS)
Apoptosis occurs through a tightly regulated cascade of caspase activation. In the context of extrinsic apoptosis, caspase-8 is activated by dimerization inside a death receptor complex, cleaved by auto-proteolysis and subsequently released into the cytosol. This fully processed form of caspase-8 is thought to cleave its substrates BID and caspase-3. To test if the release is required for substrate cleavage, we developed a novel approach based on localization probes to quantitatively characterize the spatial-temporal activity of caspases in living single cells. Our study reveals that caspase-8 is significantly more active at the plasma membrane than within the cytosol upon CD95 activation. This differential activity is controlled by the cleavage of caspase-8 prodomain. As a consequence, targeting of caspase-8 substrates to the plasma membrane can significantly accelerate cell death. Subcellular compartmentalization of caspase-8 activity may serve to restrict enzymatic activity before mitochondrial pathway activation and offers new possibilities to interfere with apoptotic sensitivity of the cells. Cell Death and Differentiation (2013) 20, 599-610; doi:10.1038/cdd.2012.156; published online 11 January 2013
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