title: The Phosphatase Dusp7 Drives Meiotic Resumption and Chromosome Alignment in Mouse Oocytes.
abstract: Mammalian oocytes are stored in the ovary, where they are arrested in prophase for prolonged periods. The mechanisms that abrogate the prophase arrest in mammalian oocytes and reinitiate meiosis are not well understood. Here, we identify and characterize an essential pathway for the resumption of meiosis that relies on the protein phosphatase DUSP7. DUSP7-depleted oocytes either fail to resume meiosis or resume meiosis with a significant delay. In the absence of DUSP7, Cdk1/CycB activity drops below the critical level required to reinitiate meiosis, precluding or delaying nuclear envelope breakdown. Our data suggest that DUSP7 drives meiotic resumption by dephosphorylating and thereby inactivating cPKC isoforms. In addition to controlling meiotic resumption, DUSP7 has a second function in chromosome segregation: DUSP7-depleted oocytes that enter meiosis show severe chromosome alignment defects and progress into anaphase prematurely. Altogether, these findings establish the phosphatase DUSP7 as an essential regulator of multiple steps in oocyte meiosis.
authors: Medical Research Council, Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Ave., Cambridge CB2 0QH, UK.
authors: Thomas
authors: T
authors: Tischer
authors: Medical Research Council, Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Ave., Cambridge CB2 0QH, UK; Max Planck Institut for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen, Germany. Electronic address: melina.schuh@mpibpc.mpg.de.
authors: Melina
authors: M
authors: Schuh
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000378:metabolism*; D056744:Cyclin B1 / Q000378:metabolism; D054637:Dual-Specificity Phosphatases / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D007527:Isoenzymes / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints; D008540:Meiosis; D051379:Mice; D009685:Nuclear Envelope / Q000378:metabolism; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D056744:Cyclin B1; D007527:Isoenzymes; D010455:Peptides; D011493:Protein Kinase C; D016203:CDC2 Protein Kinase; D054637:Dual-Specificity Phosphatases; C529383:Dusp7 protein, mouse
keywords: DUSP7; PKC; chromosome segregation; meiosis; mouse oocytes; phosphatase; prophase arrest