Plk4 and Aurora A cooperate in the initiation of acentriolar spindle assembly in mammalian oocytes

Bury, Leah, Coelho, Paula A, Simeone, Angela, Ferries, Samantha, Eyers, Claire E ORCID: 0000-0002-3223-5926, Eyers, Patrick A ORCID: 0000-0002-9220-2966, Zernicka-Goetz, Magdalena and Glover, David M (2017) Plk4 and Aurora A cooperate in the initiation of acentriolar spindle assembly in mammalian oocytes. JOURNAL OF CELL BIOLOGY, 216 (11). pp. 3571-3590.

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Abstract

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 fac-tors are postulated for the activity of multiple acentriolar microtubule organizing centers in the oocyte. We now demon-strate 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 contribut-ing to microtubule growth as the acentriolar oocyte resumes meiosis.

Item Type:	Article
Uncontrolled Keywords:	Oocytes, Cells, Cultured, Centrioles, Microtubules, Animals, Mice, Inbred C57BL, Mice, Inbred CBA, ran GTP-Binding Protein, Protein Kinase Inhibitors, Embryo Culture Techniques, Signal Transduction, Meiosis, Phosphorylation, Kinetics, Female, Aurora Kinase A, Protein Serine-Threonine Kinases
Depositing User:	Symplectic Admin
Date Deposited:	10 Jan 2018 10:29
Last Modified:	19 Jan 2023 06:46
DOI:	10.1083/jcb.201606077
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3015783