Plk4 and Aurora A cooperate in the initiation of acentriolar spindle assembly in mammalian oocytes
Autor: | David M. Glover, Claire E. Eyers, Samantha Ferries, Angela Simeone, Magdalena Zernicka-Goetz, Leah Bury, Paula A. Coelho, Patrick A. Eyers |
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Přispěvatelé: | Zernicka-Goetz, Magdalena [0000-0002-7004-2471], Glover, David [0000-0003-0956-0103], Apollo - University of Cambridge Repository |
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
PLK4 Centriole Biology Protein Serine-Threonine Kinases Microtubules Article Embryo Culture Techniques 03 medical and health sciences 0302 clinical medicine Microtubule Animals Phosphorylation Protein Kinase Inhibitors Research Articles Cells Cultured Microtubule nucleation Aurora Kinase A Centrioles Microtubule organizing center Cell Biology 3. Good health Cell biology Mice Inbred C57BL Kinetics Meiosis 030104 developmental biology ran GTP-Binding Protein Centrosome Ran Mice Inbred CBA Oocytes Female Multipolar spindles 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | The Journal of Cell Biology JOURNAL OF CELL BIOLOGY |
ISSN: | 1540-8140 0021-9525 |
Popis: | Establishing the spindle in mammalian oocytes after their prolonged arrest occurs in the absence of centrioles and is crucial for meiotic fidelity. Bury et al. show that this requires concerted activity of microtubule organizing center–associated Aurora A and Plk4, which are usually found at centrioles. Establishing the bipolar spindle in mammalian oocytes after their prolonged arrest is crucial for meiotic fidelity and subsequent development. In contrast to somatic cells, the first meiotic spindle assembles in the absence of centriole-containing centrosomes. Ran-GTP can promote microtubule nucleation near chromatin, but additional unidentified factors are postulated for the activity of multiple acentriolar microtubule organizing centers in the oocyte. We now demonstrate that partially overlapping, nonredundant functions of Aurora A and Plk4 kinases contribute to initiate acentriolar meiosis I spindle formation. Loss of microtubule nucleation after simultaneous chemical inhibition of both kinases can be significantly rescued by drug-resistant Aurora A alone. Drug-resistant Plk4 can enhance Aurora A–mediated rescue, and, accordingly, Plk4 can phosphorylate and potentiate the activity of Aurora A in vitro. Both kinases function distinctly from Ran, which amplifies microtubule growth. We conclude that Aurora A and Plk4 are rate-limiting factors contributing to microtubule growth as the acentriolar oocyte resumes meiosis. |
Databáze: | OpenAIRE |
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