title: PtdIns(3,4,5)P3 is constitutively synthesized and required for spindle translocation during meiosis in mouse oocytes.
abstract: Prior to ovulation, mammalian oocytes complete their first meiotic division and arrest at metaphase II. During this marked asymmetric cell division, the meiotic spindle moves dramatically from the center of the oocyte to the cortex to facilitate segregation of half of its chromosomal content into the diminutive first polar body. Recent investigations have documented crucial roles for filamentous actin (F-actin) in meiotic spindle translocation. However, the identity of the upstream regulators responsible for these carefully orchestrated movements has remained elusive. Utilizing fluorescently tagged probes and time-lapse confocal microscopy, we document that phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] is constitutively synthesized with spatial and temporal dynamics similar to that of F-actin and Formin 2 (Fmn2). Blockage of PtdIns(3,4,5)P3 synthesis by LY294002, a specific inhibitor of phosphoinositide 3-kinase (PI3K), disrupts cytoplasmic F-actin organization and meiotic spindle migration to the cortex. F-actin nucleator Fmn2 and Rho GTPase Cdc42 play roles in mediating the effect of PtdIns(3,4,5)P3 on F-actin assembly. Moreover, the spatial and temporal dynamics of PtdIns(3,4,5)P3 is impaired by depletion of MATER or Filia, two oocyte proteins encoded by maternal effect genes. Thus, PtdIns(3,4,5)P3 is synthesized during meiotic maturation and acts upstream of Cdc42 and Fmn2, but downstream of MATER/Filia proteins to regulate the F-actin organization and spindle translocation to the cortex during mouse oocyte meiosis.
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China. zhengp@mail.kiz.ac.cn
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.forename: Boris
authors.initials: B
authors.lastname: Baibakov
authors.forename: Xi-hong
authors.initials: XH
authors.lastname: Wang
authors.forename: Jurrien
authors.initials: J
authors.lastname: Dean
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000378:metabolism; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004527:Egg Proteins / Q000378:metabolism; D005260:Female; D000080865:Formins; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008540:Meiosis / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D009025:Morpholines / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D008941:Spindle Apparatus / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D000941:Antigens; D002867:Chromones; D004527:Egg Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009025:Morpholines; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011506:Proteins; D020764:cdc42 GTP-Binding Protein; C416503:Nalp5 protein, mouse; C532243:filia protein, mouse; C549436:formin 2 protein, mouse; C060974:phosphatidylinositol 3,4,5-triphosphate; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one