Programmed Cell Death Across the Eukaryotic Kingdoms

EU 6th Framework STREP

Research group of Pierre Golstein

Molecular mechanisms of autophagic vacuolar PCD in Dictyostelium




Fig.: Cell death in the stalk during Dictyostelium differentiation and sporulation  

The Golstein laboratory works on several PCD systems including the protist Dictyostelium that normally grows as a unicellular organism. Starvation triggers a developmental program leading to the formation of a fruiting body that includes spores and a stalk made of dead cells. Dictyostelium emerged in evolution earlier than most PCD model organisms, and possesses multiple genetic advantages (haploidy, genome sequence, several reverse genetic methods to directly link genes to functions). Golstein's group aims to further dissect the sequence of cellular and subcellular events leading to Dictyostelium cell death. Knowledge of the sequence of events in a dying cell will help to devise screening procedures to identify regulatory molecules, and define which stage is blocked by a given mutation. Current investigation, developing recent results, bears on analysis of the mode of disappearance of F-actin ( the earliest destructive event identified so far in this cell death cascade), role in cell death of  starvation-induced autophagy using autophagy gene inactivation, fate of mitochondria, and generation and analysis of a second wave of cell death resistant mutants. Dictyostelium cell death is a developmental programmed vacuolar death amenable to genetic analysis, and could prove a good model for this type of caspase-independent cell death in mammals.

Relevant References

1) Golstein et al. (2003). Cell-death alternative model organisms: why and which? Nat Rev Mol Cell Biol 4, 798-807.
2) Levraud et al. (2003) Dictyostelium cell death: early emergence and demise of highly polarized paddle cells. J Cell Biol 160, 1105-14
3) Wyllie & Golstein (2001) More than one way to go. Proc Natl Acad Sci USA 98, 11-3
4) Golstein (2000) Signal transduction. FasL binds preassembled Fas. Science 288, 2328-9
5) Olie et al. (1998) Apparent caspase independence of programmed cell death in Dictyostelium. Curr Biol 8, 955-8.

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