APPARENT CASPASE INDEPENDENCE OF PROGRAMMED CELL-DEATH IN DICTYOSTELIUM

During normal development, cell elimination [1,2] occurs by programmed cell death (PCD) [3], of which apoptosis [4] is the best known morpho logical type. Activation of cysteine proteases termed caspases [5] is required in many instances of animal PCD [6-9], but its role outside t he animal kingdom is as yet unknown. PCD occurs during developmental s tages in the slime mold Dictyostelium discoideum [10,11], Under favora ble conditions, Dictyostelium multiplies as a unicellular organism. Up on starvation, a pathway involving aggregation, differentiation and mo rphogenesis induces the formation of a multicellular fungus-like struc ture called a sorocarp [12], consisting mainly of spores and stalk cel ls, the latter being a result of cell death. Dictyostelium cell death is similar to classical apoptosis in that some cytoplasmic and chromat in condensation occurs but differs from apoptosis because it involves massive vacuolisation and, interestingly, lacks DNA fragmentation [11] , We examined whether caspase activity is required for Dictyostelium c ell death, We found that caspase inhibitors did not affect cell death, although some caspase inhibitors that did not inhibit cell death impa ired other stages in development and could block affinity-labelling of soluble extracts of Dictyostelium cells with an activated caspase-spe cific reagent. The simplest interpretation of these results is that in Dictyostelium, whether or not caspase-like molecules exist and are re quired for some developmental steps, caspase activation is not require d for cell death itself.