title: c-di-GMP induction of Dictyostelium cell death requires the polyketide DIF-1.
abstract: Cell death in the model organism Dictyostelium, as studied in monolayers in vitro, can be induced by the polyketide DIF-1 or by the cyclical dinucleotide c-di-GMP. c-di-GMP, a universal bacterial second messenger, can trigger innate immunity in bacterially infected animal cells and is involved in developmental cell death in Dictyostelium. We show here that c-di-GMP was not sufficient to induce cell death in Dictyostelium cell monolayers. Unexpectedly, it also required the DIF-1 polyketide. The latter could be exogenous, as revealed by a telling synergy between c-di-GMP and DIF-1. The required DIF-1 polyketide could also be endogenous, as shown by the inability of c-di-GMP to induce cell death in Dictyostelium HMX44A cells and DH1 cells upon pharmacological or genetic inhibition of DIF-1 biosynthesis. 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.
authors.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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Song
authors.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.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Luciani
authors.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.
authors.forename: Corinne
authors.initials: C
authors.lastname: Giusti
authors.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 golstein@ciml.univ-mrs.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Golstein
mesh_terms: D016923:Cell Death / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology; D004023:Dictyostelium / Q000166:cytology* / Q000378:metabolism; D061065:Polyketides / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction; D013045:Species Specificity
chemical_list: D061065:Polyketides; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP