title: PLK1 regulates spindle formation kinetics and APC/C activation in mouse zygote.
abstract: Polo-like kinase 1 (PLK1) is involved in essential events of cell cycle including mitosis in which it participates in centrosomal microtubule nucleation, spindle bipolarity establishment and cytokinesis. Although PLK1 function has been studied in cycling cancer cells, only limited data are known about its role in the first mitosis of mammalian zygotes. During the 1-cell stage of mouse embryo development, the acentriolar spindle is formed and the shift from acentriolar to centrosomal spindle formation progresses gradually throughout the preimplantation stage, thus providing a unique possibility to study acentriolar spindle formation. We have shown previously that PLK1 activity is not essential for entry into first mitosis, but is required for correct spindle formation and anaphase onset in 1-cell mouse embryos. In the present study, we extend this knowledge by employing quantitative confocal live cell imaging to determine spindle formation kinetics in the absence of PLK1 activity and answer the question whether metaphase arrest at PLK1-inhibited embryos is associated with low anaphase-promoting complex/cyclosome (APC/C) activity and consequently high securin level. We have shown that inhibition of PLK1 activity induces a delay in onset of acentriolar spindle formation during first mitosis. Although these PLK1-inhibited 1-cell embryos were finally able to form a bipolar spindle, not all chromosomes were aligned at the metaphase equator. PLK1-inhibited embryos were arrested in metaphase without any sign of APC/C activation with high securin levels. Our results document that PLK1 controls the onset of spindle assembly and spindle formation, and is essential for APC/C activation before anaphase onset in mouse zygotes.
authors.affiliation: Institute of Animal Physiology,Slovak Academy of Sciences,Soltesovej 4,040 01 Kosice,Slovakia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Baran
authors.affiliation: Institute of Animal Physiology and Genetics,Academy of Sciences of the Czech Republic,Libechov,Czech Republic.
authors.forename: Adela
authors.initials: A
authors.lastname: Brzakova
authors.affiliation: Institute of Animal Physiology,Slovak Academy of Sciences,Kosice,Slovakia.
authors.forename: Pavol
authors.initials: P
authors.lastname: Rehak
authors.affiliation: Institute of Animal Physiology,Slovak Academy of Sciences,Kosice,Slovakia.
authors.forename: Veronika
authors.initials: V
authors.lastname: Kovarikova
authors.affiliation: Institute of Animal Physiology and Genetics,Academy of Sciences of the Czech Republic,Libechov,Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Solc
mesh_terms: D000705:Anaphase; D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism*; D000818:Animals; D001755:Blastocyst; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D005260:Female; D007700:Kinetics; D018386:Kinetochores / Q000378:metabolism; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011621:Pteridines / Q000494:pharmacology; D008941:Spindle Apparatus / Q000378:metabolism*; D059008:Time-Lapse Imaging; D015053:Zygote / Q000187:drug effects / 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; D011621:Pteridines; D000097869:Polo-Like Kinase 1; C518477:BI 2536
keywords: APC/C; BI2536; Live cell imaging; Mouse zygote; PLK1; Securin; Spindle assembly