Programmed Cell Death Across the Eukaryotic Kingdoms

EU 6th Framework STREP

Research group of Nektarios Tavernarakis

Necrotic cell death & neurodegeneration in the worm C. elegans

Necrotic C. elegans cell




Fig.: A worm with a neurodegenerative condition  

Tavernarakis's laboratory studies both genetic and environmental insults that inflict degenerative cell death of C. elegans motor neurons and other nerve cells. For example, they have conducted extensive genetic screening to identify suppressors of degenerative cell death, and isolated mutations in several loci that bock degenerative cell death initiated by these genetic and environmental insults. The group's current focus is to characterize these mutant strains. They have recently identified two of the suppressors by cloning the corresponding genes. They genes encode two proteases, ASP-3 and ASP-4, of the Cathepsin D protease family. This is a particularly exciting finding given the role of caspases in the execution of apoptotic cell death. These results indicate that distinct proteolytic activities are involved in the destruction of a cell during degenerative cell death

Relevant References

1) Syntichaki & Tavernarakis (2003). The biochemistry of neuronal necrosis: Rogue biology? Nature Reviews Neuroscience, 4: 672-684.
2) Syntichaki et al. (2002) Specific aspartyl and calpain proteases are required for neurodegeneration in C. elegans. Nature 419, 939-44
3) Syntichaki & Tavernarakis (2002) Death by necrosis. Uncontrollable catastrophe, or is there order behind the chaos? EMBO Rep 3, 604-9
4) Xu et al. (2001) Necrotic cell death in C. elegans requires the function of calreticulin and regulators of Ca(2+) release from the endoplasmic reticulum. Neuron 31, 957-71
5) Tavernarakis et al. (2000) Heritable and inducible genetic interference by double-stranded RNA encoded by transgenes. Nature Genet 24, 180-3

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