Apparent caspase independence of programmed cell death in Dictyostelium

Abstract

During normal development, cell elimination [1,2] occurs by programmed cell death (PCD) [3], of which apoptosis [4] is the best known morphological type. Activation of cysteine proteases termed caspases [5] is required in many instances of animal PCD [6-9], but its role outside the animal kingdom is as yet unknown. PCD occurs during developmental stages in the slime mold Dictyostelium discoideum [10,11]. Under favorable conditions, Dictyostelium multiplies as a unicellular organism. Upon starvation, a pathway involving aggregation, differentiation and morphogenesis induces the formation of a multicellular fungus-like structure called a sorocarp [12], consisting mainly of spores and stalk cells, the latter being a result of cell death. Dictyostelium cell death is similar to classical apoptosis in that some cytoplasmic and chromatin 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 cell death. We found that caspase inhibitors did not affect cell death, although some caspase inhibitors that did not inhibit cell death impaired other stages in development and could block affinity-labelling of soluble extracts of Dictyostelium cells with an activated caspase-specific reagent. The simplest interpretation of these results is that in Dictyostelium, whether or not caspase-like molecules exist and are required for some developmental steps, caspase activation is not required for cell death itself.

The autophagosomal–lysosomal compartment in programmed cell death

“…Furthermore, apoptosis and autophagic cell death are not mutually exclusive phenomena, they may occur simultaneously in tissues or even, conjointly in the same cell; both processes may end, if cell residues are not phagocytosed, in secondary necrosis. It should be emphasized, that programmed cell death appears to be highly conserved during evolution as it occurs in unicellular organisms, 116 in the green algae Volvox spec regulating the germ-soma dichotomy, 117 the slime mold Dicytostelium discoideum 15,16 and, last but not least, in plants (see a series of reviews published in Cell Death and Differentiation 4(8), 1997). Golstein and coworkers raised the hypothesis that a single-core mechanism of PCD that may have emerged before the postulated multiple emergences of multicellularity has been raised.…”

“…Golstein and coworkers raised the hypothesis that a single-core mechanism of PCD that may have emerged before the postulated multiple emergences of multicellularity has been raised. 15,16 According to this hypothesis, the phenotypic variations of PCD would result from differences in enzymatic equipment and mechanical constraints adjusted to the given biological conditions. Furthermore, there is sufficient evidence to suggest that lysosomes are important mediators of programmed cell death.…”

Autophagy and cell death in model organisms

“…In addition, caspase activity is not required for Dictyostelium cell death 36 and the single Dictyostelium paracaspase gene that has been identified is not required, either for autophagic cell death or for necrotic cell death. 37,38 Therefore, apoptosis does not interfere with autophagic cell death in this organism.…”

Cross-Linking of Human FcγRIIIb Induces the Production of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor by Polymorphonuclear Neutrophils

“…Caspase-3 might be one of several different molecular pathways involved in PMN spontaneous apoptosis, so that it would be of no surprise that the CD16-induced inhibition of apoptosis remains partial. It has nevertheless been established that PCD may occur through apparently caspase-3-independent ways (65). Although it has not been clearly defined in humans, PML nuclear bodies, which are nuclear matrix-associated structures inducing a caspase-independent death process (66), might follow another pathway in PMN spontaneous apoptosis.…”