Limits...
c-di-GMP induction of Dictyostelium cell death requires the polyketide DIF-1.

Song Y, Luciani MF, Giusti C, Golstein P - Mol. Biol. Cell (2014)

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.

View Article: PubMed Central - PubMed

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

Related in: MedlinePlus

Inhibition of the endogenous DIF-1 biosynthetic pathway prevented vacuolization by exogenous c-di-GMP. (A) Pharmacological inhibition of polyketide synthesis by cerulenin added to DH1 cells at the indicated concentration as soon as the beginning of starvation and for the whole duration of the experiment. Cells were examined 40 h after addition of DIF-1 and/or c-di-GMP. (B) In a separate experiment, DH1 parental and DH1.stlB− mutant cells were examined 22 and 40 h after addition of DIF-1 and/or c-di-GMP. Numbers are percentages of vacuolization as in the legend to Figure 1A. Cerulenin or the stlB mutation prevented c-di-GMP–induced vacuolization, showing that it required an stlB-dependent polyketide. Similar results were obtained with another independently obtained stlB− mutant clone.
© Copyright Policy - creative-commons
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4325836&req=5

Figure 3: Inhibition of the endogenous DIF-1 biosynthetic pathway prevented vacuolization by exogenous c-di-GMP. (A) Pharmacological inhibition of polyketide synthesis by cerulenin added to DH1 cells at the indicated concentration as soon as the beginning of starvation and for the whole duration of the experiment. Cells were examined 40 h after addition of DIF-1 and/or c-di-GMP. (B) In a separate experiment, DH1 parental and DH1.stlB− mutant cells were examined 22 and 40 h after addition of DIF-1 and/or c-di-GMP. Numbers are percentages of vacuolization as in the legend to Figure 1A. Cerulenin or the stlB mutation prevented c-di-GMP–induced vacuolization, showing that it required an stlB-dependent polyketide. Similar results were obtained with another independently obtained stlB− mutant clone.

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?


c-di-GMP induction of Dictyostelium cell death requires the polyketide DIF-1.

Song Y, Luciani MF, Giusti C, Golstein P - Mol. Biol. Cell (2014)

Inhibition of the endogenous DIF-1 biosynthetic pathway prevented vacuolization by exogenous c-di-GMP. (A) Pharmacological inhibition of polyketide synthesis by cerulenin added to DH1 cells at the indicated concentration as soon as the beginning of starvation and for the whole duration of the experiment. Cells were examined 40 h after addition of DIF-1 and/or c-di-GMP. (B) In a separate experiment, DH1 parental and DH1.stlB− mutant cells were examined 22 and 40 h after addition of DIF-1 and/or c-di-GMP. Numbers are percentages of vacuolization as in the legend to Figure 1A. Cerulenin or the stlB mutation prevented c-di-GMP–induced vacuolization, showing that it required an stlB-dependent polyketide. Similar results were obtained with another independently obtained stlB− mutant clone.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4325836&req=5

Figure 3: Inhibition of the endogenous DIF-1 biosynthetic pathway prevented vacuolization by exogenous c-di-GMP. (A) Pharmacological inhibition of polyketide synthesis by cerulenin added to DH1 cells at the indicated concentration as soon as the beginning of starvation and for the whole duration of the experiment. Cells were examined 40 h after addition of DIF-1 and/or c-di-GMP. (B) In a separate experiment, DH1 parental and DH1.stlB− mutant cells were examined 22 and 40 h after addition of DIF-1 and/or c-di-GMP. Numbers are percentages of vacuolization as in the legend to Figure 1A. Cerulenin or the stlB mutation prevented c-di-GMP–induced vacuolization, showing that it required an stlB-dependent polyketide. Similar results were obtained with another independently obtained stlB− mutant clone.
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?

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.

View Article: PubMed Central - PubMed

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
Related in: MedlinePlus