title: Autophagy is used as a survival program in unfertilized sea urchin eggs that are destined to die by apoptosis after inactivation of MAPK1/3 (ERK2/1).
abstract: A high MAPK1/3 (also known as ERK2/1, respectively) activity, preventing spontaneous activation, is essential to maintain cell cycle arrest of mature oocytes of mammals, frogs or invertebrates such as starfish. Mature oocytes would undergo a "suicide"-like cell death if not fertilized. We previously have reported that downregulation of MAPK1/3 in unfertilized sea urchin eggs induces a calcium-dependent entry into mitosis. We show here that this event is followed by a series of pseudo-mitotic cell cycles associated with transient Cai increases, preceding CASP3/caspase-3 activation and apoptosis. However, cell death was delayed after inhibition of the Cai transients or of cyclin-dependent kinases (CDK), with roscovitine. In these conditions, eggs enter an autophagy program as suggested by detection of processed LC3B by western blot, immunofluorescence and immunogold staining, visualization of autophagy vesicles by electron microscopy, and an increase in acidic vesicular organelles (AVOs). We found that bafilomycin A 1 or an association of leupeptin and pepstatin, which are widely used to study autophagy, may act upon calcium signaling or cell cycle events, respectively, and not only on autophagy events. Finally, inhibition of PtdIns 3-kinase with wortmannin or LY294002 powerfully stimulated cell death of unfertilized eggs, which suggests that this activity does not negatively regulate autophagy as is often reported, but rather stimulates survival in unfertilized eggs. We suggest that apoptosis of unfertilized eggs is the consequence of an aberrant short attempt of development that occurs if MAPK1/3 is inactivated, but these eggs can use autophagy as a survival program when the cell cycle is blocked.
authors: Centre de Neurosciences Paris-Sud (CNPS); CNRS UMR 8195; Université Paris XI; Orsay, France.
authors: Ludivine
authors: L
authors: Houel-Renault
authors: Centre de Neurosciences Paris-Sud (CNPS); CNRS UMR 8195; Université Paris XI; Orsay, France.
authors: Laetitia
authors: L
authors: Philippe
authors: Centre de Neurosciences Paris-Sud (CNPS); CNRS UMR 8195; Université Paris XI; Orsay, France.
authors: Marion
authors: M
authors: Piquemal
authors: Centre de Neurosciences Paris-Sud (CNPS); CNRS UMR 8195; Université Paris XI; Orsay, France.
authors: Brigitte
authors: B
authors: Ciapa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004789:Enzyme Activation; D005306:Fertilization / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D010063:Ovum; D019869:Phosphatidylinositol 3-Kinases; D012617:Sea Urchins
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D018844:Cyclin-Dependent Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: MAP kinase; MAPK1/3; PtdIns 3-kinase; apoptosis; autophagy; bafilomycin A1; calcium; cell cycle; egg; leupeptin; mitosis; oocyte; sea urchin