title: Role of Greatwall kinase in release of mouse oocytes from diplotene arrest.
abstract: In eukaryotes, mitosis entry is induced by activation of maturation-promoting factor (MPF), which is regulated by a network of kinases and phosphatases. It has been suggested that Greatwall (GWL) kinase was crucial for the M-phase entry and could maintain cyclin B-Cdc2 activity through regulation of protein phosphatase 2A (PP2A), a counteracting phosphatase of MPF. Here, the role of GWL was assessed during release of mouse oocytes from prophase I arrest. GWL was crucial for meiotic maturation in mouse oocytes. As a positive regulator for meiosis resumption, GWL was continually expressed in germinal vesicle (GV) and MII stage oocytes and two-cell stage embryos. Additionally, GWL localized to the nucleus and dispersed into cytoplasm during GV breakdown (GVBD). Furthermore, downregulation of GWL or overexpression of catalytically-inactive GWL inhibited partial meiotic maturation. This prophase I arrest induced by GWL depletion could be rescued by the PP2A inhibition. However, both GWL-depleted and rescued oocytes had severe spindle defects that hardly reached MII. In contrast, oocytes overexpressing wild-type GWL resumed meiosis and progressed to MII stage. Thus, our data demonstrate that GWL acts in a pathway with PP2A which is essential for prophase I exit and metaphase I microtubule assembly in mouse oocytes.
authors.affiliation: Department of Biochemical and Molecular Biology, China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zhao
authors.forename: Dahai
authors.initials: D
authors.lastname: Yu
authors.forename: Chen
authors.initials: C
authors.lastname: Feng
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.forename: Didi
authors.initials: D
authors.lastname: Wu
authors.forename: Minglin
authors.initials: M
authors.lastname: Jin
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
authors.forename: Xiuxia
authors.initials: X
authors.lastname: Wang
authors.forename: Bingzhi
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D049469:Meiotic Prophase I / Q000502:physiology*; D000090204:Mesothelin; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism
chemical_list: D019926:Cyclin B; D008869:Microtubule-Associated Proteins; C000715528:Msln protein, mouse; D017346:Protein Serine-Threonine Kinases; C585164:greatwall protein, mouse; D016203:CDC2 Protein Kinase; D054648:Protein Phosphatase 2; D000090204:Mesothelin
keywords: Greatwall; maturation-promoting factor; meiotic maturation; oocyte; protein phosphatase