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
Mentions: To check in DH1 cells (for consistency with the aforementioned mutants) whether DIF-1 or other polyketides were required for c-di-GMP–induced cell death, we first used cerulenin, known to inhibit the biosynthesis of polyketides, including that of DIF-1 (Kay, 1998; Serafimidis and Kay, 2005). Cerulenin, as expected, did not impair vacuolization induced by exogenous DIF-1 (and thus did not impair vacuolization as such), but, remarkably, almost completely prevented induction of vacuolization by exogenous c-di-GMP (Figure 3A). This indicated that one or several cerulenin-inhibitable moieties were required together with c-di-GMP for induction of cell death. Cerulenin inhibits the β-keto-acyl domain of polyketide synthases, including in Dictyostelium not only the StlB polyketide synthase (Austin et al., 2006; Saito et al., 2008) required for the biosynthesis of the THPH precursor of DIF-1, but also the StlA polyketide synthase, plus close to 40 other polyketide synthases, including two fatty acid synthases (Chance et al., 1976; Omura, 1976; Kridel et al., 2007; Zucko et al., 2007; Narita et al., 2014). What is the polyketide synthase catalyzing the synthesis of molecules required for c-di-GMP–induced cell death?
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.