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Genetic Interactions between the Aurora Kinases Reveal New Requirements for AURKB and AURKC during Oocyte Meiosis.

Current biology : CB | 2018

Errors in chromosome segregation during female meiosis I occur frequently, and aneuploid embryos account for 1/3 of all miscarriages in humans [1]. Unlike mitotic cells that require two Aurora kinase (AURK) homologs to help prevent aneuploidy (AURKA and AURKB), mammalian germ cells also require a third (AURKC) [2, 3]. AURKA is the spindle-pole-associated homolog, and AURKB/C are the chromosome-localized homologs. In mitosis, AURKB has essential roles as the catalytic subunit of the chromosomal passenger complex (CPC), regulating chromosome alignment, kinetochore-microtubule attachments, cohesion, the spindle assembly checkpoint, and cytokinesis [4, 5]. In mouse oocyte meiosis, AURKC takes over as the predominant CPC kinase [6], although the requirement for AURKB remains elusive [7]. In the absence of AURKC, AURKB compensates, making defining potential non-overlapping functions difficult [6, 8]. To investigate the role(s) of AURKB and AURKC in oocytes, we analyzed oocyte-specific Aurkb and Aurkc single- and double-knockout (KO) mice. Surprisingly, we find that double KO female mice are fertile. We demonstrate that, in the absence of AURKC, AURKA localizes to chromosomes in a CPC-dependent manner. These data suggest that AURKC prevents AURKA from localizing to chromosomes by competing for CPC binding. This competition is important for adequate spindle length to support meiosis I. We also describe a unique requirement for AURKB to negatively regulate AURKC to prevent aneuploidy. Together, our work reveals oocyte-specific roles for the AURKs in regulating each other's localization and activity. This inter-kinase regulation is critical to support wild-type levels of fecundity in female mice.

Pubmed ID: 30415701 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

Associated grants

  • Agency: NICHD NIH HHS, United States
    Id: F31 HD089597
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM112801

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


QIAGEN (tool)

RRID:SCR_008539

A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.

View all literature mentions

Aurora A Antibody (antibody)

RRID:AB_221398

This unknown targets Aurora A

View all literature mentions

Phospho-Aurora A (Thr288)/Aurora B (Thr232)/Aurora C (Thr198) (D13A11) XP Rabbit mAb (antibody)

RRID:AB_2061631

This monoclonal targets Phospho-Aurora A (Thr288)/Aurora B (Thr232)/Aurora C (Thr198

View all literature mentions

α-Tubulin (11H10) Rabbit mAb (antibody)

RRID:AB_2619646

This monoclonal targets alpha-Tubulin

View all literature mentions

Anti-phospho-Histone H3 (Ser10), clone 3H10 (antibody)

RRID:AB_310016

This monoclonal targets phospho-Histone H3 (Ser10) clone 3H10

View all literature mentions

Phospho-Aurora A (Thr288) (C39D8) Rabbit mAb (antibody)

RRID:AB_2061481

This monoclonal targets Human Aurora A, phospho (Thr288)

View all literature mentions

H3-celegans (antibody)

RRID:AB_302613

This polyclonal targets H3

View all literature mentions

Monoclonal Anti-alpha-Tubulin antibody produced in mouse (antibody)

RRID:AB_477582

This monoclonal targets alpha-Tubulin antibody produced in mouse

View all literature mentions

Anti-Centromere Antibody (antibody)

RRID:AB_2687472

This polyclonal targets Centromere

View all literature mentions

Hec1 (phospho Ser 55) antibody (antibody)

RRID:AB_11162004

This polyclonal targets Hec1 (phospho Ser 55)

View all literature mentions

Adobe Illustrator (software resource)

RRID:SCR_010279

Vector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.

View all literature mentions

STOCK Tg(Gdf9-icre)5092Coo/J (organism)

RRID:IMSR_JAX:011062

Mus musculus with name STOCK Tg(Gdf9-icre)5092Coo/J from IMSR.

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B6D2F1/J (organism)

RRID:IMSR_JAX:100006

Mus musculus with name B6D2F1/J from IMSR.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

View all literature mentions

ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

View all literature mentions

Adobe Illustrator (software resource)

RRID:SCR_010279

Vector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.

View all literature mentions

GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

View all literature mentions

ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

View all literature mentions

STOCK Tg(Gdf9-icre)5092Coo/J (organism)

RRID:IMSR_JAX:011062

Mus musculus with name STOCK Tg(Gdf9-icre)5092Coo/J from IMSR.

View all literature mentions

B6D2F1/J (organism)

RRID:IMSR_JAX:100006

Mus musculus with name B6D2F1/J from IMSR.

View all literature mentions

Phospho-Aurora A (Thr288)/Aurora B (Thr232)/Aurora C (Thr198) (D13A11) XP Rabbit mAb (antibody)

RRID:AB_2061631

This monoclonal targets Phospho-Aurora A (Thr288)/Aurora B (Thr232)/Aurora C (Thr198

View all literature mentions

Hec1 (phospho Ser 55) antibody (antibody)

RRID:AB_11162004

This polyclonal targets Hec1 (phospho Ser 55)

View all literature mentions

Phospho-Aurora A (Thr288) (C39D8) Rabbit mAb (antibody)

RRID:AB_2061481

This monoclonal targets Human Aurora A, phospho (Thr288)

View all literature mentions

Anti-phospho-Histone H3 (Ser10), clone 3H10 (antibody)

RRID:AB_310016

This monoclonal targets phospho-Histone H3 (Ser10) clone 3H10

View all literature mentions

Aurora A Antibody (antibody)

RRID:AB_221398

This unknown targets Aurora A

View all literature mentions

α-Tubulin (11H10) Rabbit mAb (antibody)

RRID:AB_2619646

This monoclonal targets alpha-Tubulin

View all literature mentions

Monoclonal Anti-alpha-Tubulin antibody produced in mouse (antibody)

RRID:AB_477582

This monoclonal targets alpha-Tubulin antibody produced in mouse

View all literature mentions

H3-celegans (antibody)

RRID:AB_302613

This polyclonal targets H3

View all literature mentions

Anti-Centromere Antibody (antibody)

RRID:AB_2687472

This polyclonal targets Centromere

View all literature mentions