c-di-GMP induction of Dictyostelium cell death requires the polyketide DIF-1.
Bottom Line: In these cases, c-di-GMP-induced cell death was rescued by complementation with exogenous DIF-1.Taken together, these results demonstrated that c-di-GMP could trigger cell death in Dictyostelium only in the presence of the DIF-1 polyketide or its metabolites.This identified another element of control to this cell death and perhaps also to c-di-GMP effects in other situations and organisms.
Affiliation: Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université; Institut National de la Santé et de la Recherche Médicale, U1104; and Centre National de la Recherche Scientifique, UMR7280, 13288 Marseille, France.Show MeSH
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Mentions: Induction in vitro by DIF-1 or by c-di-GMP led to cell death with similar subcellular lesions, such as vacuolization and synthesis of cellulose cell encasings (Levraud et al., 2003; Giusti et al., 2009; unpublished data). However, in Dictyostelium cells of the DH1 strain, whereas vacuolization induced by DIF-1 was prevented by the talB (Giusti et al., 2009), iplA (Lam et al., 2008), and DhkMins (Giusti et al., 2010) mutations (Figure 1A, second column), vacuolization induced by exogenous c-di-GMP was not prevented by these mutations (Figure 1A, third column). Consistently, these mutations prevented cell death (defined here as the inability of cells to regrow upon addition of rich medium) induced by DIF-1 but not that induced by exogenous c-di-GMP (Figure 1B; unpublished data). In this article, exogenous means experimentally added to the cells under test, and endogenous means produced by (some of) the cells under test and acting on the same or other cells. Similarly, cyclosporin A inhibited vacuolization and cell death induced by DIF-1 (Lam et al., 2008) but not by c-di-GMP (Supplemental Figure S1). In addition, as in other Dictyostelium strains (Huang et al., 2006; Zhukovskaya et al., 2006), in DH1 cells, the bZip transcription factor DimB translocated from the cytosol to the nucleus in a matter of minutes after addition of DIF-1 (with or without c-di-GMP; Figure 1C) but not after addition of c-di-GMP (Figure 1C). Taken together, these differences indicated that at least parts of the pathways to cell death induced by exogenous DIF-1 and exogenous c-di-GMP were distinct.
Affiliation: Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université; Institut National de la Santé et de la Recherche Médicale, U1104; and Centre National de la Recherche Scientifique, UMR7280, 13288 Marseille, France.