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

Bury, Leah and Coelho, Paula A. and Simeone, Angela and Ferries, Samantha and Eyers, Claire E. and Eyers, Patrick A. and 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. ISSN 0021-9525. PMCID PMC5674873. doi:10.1083/jcb.201606077. https://resolver.caltech.edu/CaltechAUTHORS:20190408-162605585

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[img] Image (JPEG) (Figure 1. Plk4 localizes to MTOCs in the mouse oocyte and facilitates microtubule growth upon resumption of meiosis) - Supplemental Material
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[img] Image (JPEG) (Figure 2. Aurora A, Plk4, or Plk1 inhibition differently affect meiosis I progression) - Supplemental Material
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[img] Image (JPEG) (Figure 3. Aurora A, but not Plk1, is required for microtubule growth upon NEBD during mouse oocyte meiosis I) - Supplemental Material
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[img] Image (JPEG) (Figure 4. Aurora A activity is required for the correct size and number of MTOCs in oocytes) - Supplemental Material
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[img] Image (JPEG) (Figure 5. Requirement for Aurora A predominates over Plk4 to initiate microtubule nucleation) - Supplemental Material
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[img] Image (JPEG) (Figure 6. Ran, Plk4, and Aurora A cooperate to promote bipolar spindle assembly) - Supplemental Material
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[img] Image (JPEG) (Figure 7. Ran has distinct functions from Aurora A and Plk4 during assembly of a meiosis I spindle) - Supplemental Material
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[img] Image (JPEG) (Figure 8. Cooperation among Ran, Aurora A, and Plk4 in regulating bivalent movement and congression toward the metaphase I plate) - Supplemental Material
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[img] Image (JPEG) (Figure 9. Temporal and spatial analysis of Aurora, Plk4 and RAN in the early steps of microtubule growth and dynamics) - Supplemental Material
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[img] Image (JPEG) (Figure 10. Meiosis I spindle formation is a result of Aurora A, Plk4, and Ran-GTP activity) - Supplemental Material
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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 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1083/jcb.201606077DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674873/PubMed CentralArticle
ORCID:
AuthorORCID
Bury, Leah0000-0002-6218-2837
Coelho, Paula A.0000-0003-0614-7575
Eyers, Claire E.0000-0002-3223-5926
Eyers, Patrick A.0000-0002-9220-2966
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Glover, David M.0000-0003-0956-0103
Additional Information:© 2017 Bury et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). Submitted: June 15, 2016. Revision received June 27, 2017. Accepted: August 9, 2017. Published September 28, 2017. We are grateful to Andrew K. Shiau and Karen Oegema as well as to the Ludwig Small Molecule Discovery Group for valuable help and for providing the Plk4 inhibitor centrinone. We would also like to thank Anthony A. Hyman, Laurence Pelletier, and Jantina A. Manning for reagents, antibodies, and constructs; Jonathon Pines, Melina Schuh, Dean Clift, and Bedra Sharif for assistance and advice; and Kevin O’Holleran from the Cambridge Advanced Imaging Centre for help and assistance with FRAP experiments. This research has been regulated under the Animals (Scientific Procedures) Act 1986 Amendment Regulations 2012 following ethical review by the University of Cambridge Animal Welfare and Ethical Review Body. L. Bury was the recipient of a Cancer Research UK research studentship from Cambridge Cancer Centre. P.A. Coelho is supported by Cancer Research UK program grant C3/A18795 to D.M. Glover. M. Zernicka-Goetz is a Wellcome Trust Senior Fellow. P.A. Eyers acknowledges North West Cancer Research for additional support (grants CR1037 and CR1088). Author contributions: L. Bury designed and performed all experiments except those indicated below and contributed to writing the manuscript. P.A. Coelho carried out the FRAP experiments and contributed to writing the manuscript. A. Simeone carried out statistical analysis. S. Ferries, C.E. Eyers, and P.A. Eyers carried out analyses of phosphorylation of Aurora A by Plk4 in Fig. S5. M. Zernicka-Goetz co-supervised the project. D.M. Glover supervised the project and wrote the manuscript. The authors declare no competing financial interests.
Funders:
Funding AgencyGrant Number
Cancer Research UKC3/A18795
Wellcome TrustUNSPECIFIED
North West Cancer Research FundCR1037
North West Cancer Research FundCR1088
Issue or Number:11
PubMed Central ID:PMC5674873
DOI:10.1083/jcb.201606077
Record Number:CaltechAUTHORS:20190408-162605585
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190408-162605585
Official Citation:Plk4 and Aurora A cooperate in the initiation of acentriolar spindle assembly in mammalian oocytes Leah Bury, Paula A. Coelho, Angela Simeone, Samantha Ferries, Claire E. Eyers, Patrick A. Eyers, Magdalena Zernicka-Goetz, David M. Glover J Cell Biol Nov 2017, 216 (11) 3571-3590; DOI: 10.1083/jcb.201606077
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94575
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:09 Apr 2019 15:46
Last Modified:16 Nov 2021 17:06

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