title: MAP kinases regulate unfertilized egg apoptosis and fertilization suppresses death via Ca2+ signaling.
abstract: The default fate for eggs from many species is death by apoptosis and thus, successful fertilization depends upon suppression of the maternal death program. Little is known about the molecular triggers which activate this process or how the fertilization signal suppresses the default maternal apoptotic pathway. The MAP kinase (MAPK) family member, ERK, plays a universal and critical role in several stages of oocyte meiotic maturation, and fertilization results in ERK inactivation. In somatic cells, ERK and other MAPK family members, p38 and JNK, provide opposing signals to regulate apoptosis, however, it is not known whether MAPKs play a regulatory role in egg apoptosis, nor whether suppression of apoptosis by fertilization is mediated by MAPK activity. Here we demonstrate that MAPKs are involved in starfish egg apoptosis and we investigate the relationship between the fertilization induced signaling pathway and MAPK activation. ERK is active in post-meiotic eggs just until apoptosis onset and then p38, JNK and a third kinase are activated, and remain active through execution. Sequential activation of ERK and p38 is necessary for apoptosis, and newly synthesized proteins are required both upstream of ERK and downstream of p38 for activation of the full apoptotic program. Fertilization causes a dramatic rise in intracellular Ca2+, and we report that Ca2+ provides a necessary and sufficient pro-survival signal. The Ca2+ pathway following fertilization of both young and aged eggs causes ERK to be rapidly inactivated, but fertilization cannot rescue aged eggs from death, indicating that ERK inactivation is not sufficient to suppress apoptosis.
authors.affiliation: Department of Molecular Biology and Genetics, Bosphorus University, Istanbul, Turkey. kirsten_sadler_phd98@post.harvard.edu
authors.forename: Kirsten C
authors.initials: KC
authors.lastname: Sadler
authors.forename: Ozlem
authors.initials: O
authors.lastname: Yüce
authors.forename: Fisun
authors.initials: F
authors.lastname: Hamaratoglu
authors.forename: Valérie
authors.initials: V
authors.lastname: Vergé
authors.forename: Gérard
authors.initials: G
authors.lastname: Peaucellier
authors.forename: André
authors.initials: A
authors.lastname: Picard
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D005260:Female; D005306:Fertilization / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D010063:Ovum / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013215:Starfish / Q000502:physiology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium