title: Autophagic cell death in Dictyostelium requires the receptor histidine kinase DhkM.
abstract: Dictyostelium constitutes a genetically tractable model for the analysis of autophagic cell death (ACD). During ACD, Dictyostelium cells first transform into paddle cells and then become round, synthesize cellulose, vacuolize, and die. Through random insertional mutagenesis, we identified the receptor histidine kinase DhkM as being essential for ACD. Surprisingly, different DhkM mutants showed distinct nonvacuolizing ACD phenotypes. One class of mutants arrested ACD at the paddle cell stage, perhaps through a dominant-negative effect. Other mutants, however, progressed further in the ACD program. They underwent rounding and cellulose synthesis but stopped before vacuolization. Moreover, they underwent clonogenic but not morphological cell death. Exogenous 8-bromo-cAMP restored vacuolization and death. A role for a membrane receptor at a late stage of the ACD pathway is puzzling, raising questions as to which ligand it is a receptor for and which moieties it phosphorylates. Together, DhkM is the most downstream-known molecule required for this model ACD, and its distinct mutants genetically separate previously undissociated late cell death events.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, Marseille F-13288, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Giusti
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Luciani
authors.forename: Sarina
authors.initials: S
authors.lastname: Ravens
authors.forename: Alexandre
authors.initials: A
authors.lastname: Gillet
authors.forename: Pierre
authors.initials: P
authors.lastname: Golstein
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D002482:Cellulose / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D000071677:Histidine Kinase; D016254:Mutagenesis, Insertional; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000199:Actins; D015800:Protozoan Proteins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002482:Cellulose; D011494:Protein Kinases; D000071677:Histidine Kinase