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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.

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Recapitulation of some of the results on DIF-1 and c-di-GMP pathways inducing Dictyostelium cell death in monolayers. (A) TalinB− mutant cells were incubated or not with 50 μM cerulenin and with or without 100 nM DIF-1 and 10 μM c-di-GMP for 40 h. See the text for comments on the results. (B) Tentative representation of DIF-1 and c-di-GMP pathways inducing Dictyostelium cell death in vitro, with some of the mutations and drugs mentioned in this work. Bottom, a first signal—starvation plus cAMP—triggers autophagy and sensitizes cells to the second signal. Top, second signals would operate only on cells sensitized by the first signal. Exogenous DIF-1 triggers an autonomous pathway to cell death marked by several mutations. To induce cell death, exogenous c-di-GMP requires cooperation with endogenously synthesized (or exogenous, not represented) DIF-1. Middle, DIF-1 biosynthetic pathway, marked by other mutations, induced by cAMP, provides endogenous DIF-1 required for cooperation with exogenous c-di-GMP to induce cell death. We have not represented the iplA− mutation, which could inhibit both the exogenous autonomous DIF-1 pathway and exogenous DIF-1 cooperation.
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Figure 5: Recapitulation of some of the results on DIF-1 and c-di-GMP pathways inducing Dictyostelium cell death in monolayers. (A) TalinB− mutant cells were incubated or not with 50 μM cerulenin and with or without 100 nM DIF-1 and 10 μM c-di-GMP for 40 h. See the text for comments on the results. (B) Tentative representation of DIF-1 and c-di-GMP pathways inducing Dictyostelium cell death in vitro, with some of the mutations and drugs mentioned in this work. Bottom, a first signal—starvation plus cAMP—triggers autophagy and sensitizes cells to the second signal. Top, second signals would operate only on cells sensitized by the first signal. Exogenous DIF-1 triggers an autonomous pathway to cell death marked by several mutations. To induce cell death, exogenous c-di-GMP requires cooperation with endogenously synthesized (or exogenous, not represented) DIF-1. Middle, DIF-1 biosynthetic pathway, marked by other mutations, induced by cAMP, provides endogenous DIF-1 required for cooperation with exogenous c-di-GMP to induce cell death. We have not represented the iplA− mutation, which could inhibit both the exogenous autonomous DIF-1 pathway and exogenous DIF-1 cooperation.

Mentions: In contrast to DH1 cells, Dictyostelium HMX44A cells could be induced to die by DIF-1 but not by c-di-GMP. In separate experiments, DH1- or HMX44A-starved cells were subjected to either 100 nM DIF-1 or 10 μM c-di-GMP (A) for 40 h and then photographed (see Figure 1A legend for details) or (B) for 24 h and then subjected to HL5 medium to allow regrowth of surviving cells; regrown cells were counted after 3 more days (see Figure 1B legend for details). (C) HMX44A cells were subjected in LabTek chambers to graded concentrations of DIF-1 and c-di-GMP in a checkerboard manner. The numbers are the percentages of clumps each comprising at least three vacuolized cells after 17 h in the presence or absence of inducers, established as in the legend to Figure 1A. HMX44A cells showed vacuolization when subjected to DIF-1 alone but not to c-di-GMP alone, and there was synergy between the two inducers. These cells made no endogenous DIF-1, leading to no vacuolization by exogenous c-di-GMP. However, addition of exogenous DIF-1 led to vacuolization through the autonomous DIF-1 pathway and through cooperation with exogenous c-di-GMP (see Figure 5 for schematization).


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)

Recapitulation of some of the results on DIF-1 and c-di-GMP pathways inducing Dictyostelium cell death in monolayers. (A) TalinB− mutant cells were incubated or not with 50 μM cerulenin and with or without 100 nM DIF-1 and 10 μM c-di-GMP for 40 h. See the text for comments on the results. (B) Tentative representation of DIF-1 and c-di-GMP pathways inducing Dictyostelium cell death in vitro, with some of the mutations and drugs mentioned in this work. Bottom, a first signal—starvation plus cAMP—triggers autophagy and sensitizes cells to the second signal. Top, second signals would operate only on cells sensitized by the first signal. Exogenous DIF-1 triggers an autonomous pathway to cell death marked by several mutations. To induce cell death, exogenous c-di-GMP requires cooperation with endogenously synthesized (or exogenous, not represented) DIF-1. Middle, DIF-1 biosynthetic pathway, marked by other mutations, induced by cAMP, provides endogenous DIF-1 required for cooperation with exogenous c-di-GMP to induce cell death. We have not represented the iplA− mutation, which could inhibit both the exogenous autonomous DIF-1 pathway and exogenous DIF-1 cooperation.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 5: Recapitulation of some of the results on DIF-1 and c-di-GMP pathways inducing Dictyostelium cell death in monolayers. (A) TalinB− mutant cells were incubated or not with 50 μM cerulenin and with or without 100 nM DIF-1 and 10 μM c-di-GMP for 40 h. See the text for comments on the results. (B) Tentative representation of DIF-1 and c-di-GMP pathways inducing Dictyostelium cell death in vitro, with some of the mutations and drugs mentioned in this work. Bottom, a first signal—starvation plus cAMP—triggers autophagy and sensitizes cells to the second signal. Top, second signals would operate only on cells sensitized by the first signal. Exogenous DIF-1 triggers an autonomous pathway to cell death marked by several mutations. To induce cell death, exogenous c-di-GMP requires cooperation with endogenously synthesized (or exogenous, not represented) DIF-1. Middle, DIF-1 biosynthetic pathway, marked by other mutations, induced by cAMP, provides endogenous DIF-1 required for cooperation with exogenous c-di-GMP to induce cell death. We have not represented the iplA− mutation, which could inhibit both the exogenous autonomous DIF-1 pathway and exogenous DIF-1 cooperation.
Mentions: In contrast to DH1 cells, Dictyostelium HMX44A cells could be induced to die by DIF-1 but not by c-di-GMP. In separate experiments, DH1- or HMX44A-starved cells were subjected to either 100 nM DIF-1 or 10 μM c-di-GMP (A) for 40 h and then photographed (see Figure 1A legend for details) or (B) for 24 h and then subjected to HL5 medium to allow regrowth of surviving cells; regrown cells were counted after 3 more days (see Figure 1B legend for details). (C) HMX44A cells were subjected in LabTek chambers to graded concentrations of DIF-1 and c-di-GMP in a checkerboard manner. The numbers are the percentages of clumps each comprising at least three vacuolized cells after 17 h in the presence or absence of inducers, established as in the legend to Figure 1A. HMX44A cells showed vacuolization when subjected to DIF-1 alone but not to c-di-GMP alone, and there was synergy between the two inducers. These cells made no endogenous DIF-1, leading to no vacuolization by exogenous c-di-GMP. However, addition of exogenous DIF-1 led to vacuolization through the autonomous DIF-1 pathway and through cooperation with exogenous c-di-GMP (see Figure 5 for schematization).

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.

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