title: Multiple requirements of PLK1 during mouse oocyte maturation.
abstract: Polo-like kinase 1 (PLK1) orchestrates multiple events of cell division. Although PLK1 function has been intensively studied in centriole-containing and rapidly cycling somatic cells, much less is known about its function in the meiotic divisions of mammalian oocytes, which arrest for a long period of time in prophase before meiotic resumption and lack centrioles for spindle assembly. Here, using specific small molecule inhibition combined with live mouse oocyte imaging, we comprehensively characterize meiotic PLK1's functions. We show that PLK1 becomes activated at meiotic resumption on microtubule organizing centers (MTOCs) and later at kinetochores. PLK1 is required for efficient meiotic resumption by promoting nuclear envelope breakdown. PLK1 is also needed to recruit centrosomal proteins to acentriolar MTOCs to promote normal spindle formation, as well as for stable kinetochore-microtubule attachment. Consequently, PLK1 inhibition leads to metaphase I arrest with misaligned chromosomes activating the spindle assembly checkpoint (SAC). Unlike in mitosis, the metaphase I arrest is not bypassed by the inactivation of the SAC. We show that PLK1 is required for the full activation of the anaphase promoting complex/cyclosome (APC/C) by promoting the degradation of the APC/C inhibitor EMI1 and is therefore essential for entry into anaphase I. Moreover, our data suggest that PLK1 is required for proper chromosome segregation and the maintenance of chromosome condensation during the meiosis I-II transition, independently of the APC/C. Thus, our results define the meiotic roles of PLK1 in oocytes and reveal interesting differential requirements of PLK1 between mitosis and oocyte meiosis in mammals.
authors: Institute of Animal Physiology and Genetics, Libechov, Czech Republic.
authors: Petr
authors: P
authors: Solc
authors: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany; Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology, Kobe, Japan.
authors: Tomoya S
authors: TS
authors: Kitajima
authors: Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology, Kobe, Japan.
authors: Shuhei
authors: S
authors: Yoshida
authors: Institute of Animal Physiology and Genetics, Libechov, Czech Republic.
authors: Adela
authors: A
authors: Brzakova
authors: Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology, Kobe, Japan.
authors: Masako
authors: M
authors: Kaido
authors: Institute of Animal Physiology, Kosice, Slovakia.
authors: Vladimir
authors: V
authors: Baran
authors: Institute of Animal Physiology and Genetics, Libechov, Czech Republic.
authors: Alexandra
authors: A
authors: Mayer
authors: Institute of Animal Physiology and Genetics, Libechov, Czech Republic.
authors: Pavlina
authors: P
authors: Samalova
authors: Institute of Animal Physiology and Genetics, Libechov, Czech Republic.
authors: Jan
authors: J
authors: Motlik
authors: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors: Jan
authors: J
authors: Ellenberg
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D020090:Chromosome Segregation / Q000502:physiology; D005260:Female; D007091:Image Processing, Computer-Assisted; D018386:Kinetochores / Q000378:metabolism; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D018613:Microscopy, Confocal; D022101:Microtubule-Organizing Center / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism; D009865:Oocytes / Q000254:growth & development*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D064173:Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1