Aurora kinase A is essential for meiosis in mouse oocytes.

Cecilia S Blengini,Patricia Ibrahimian,Michaela Vaskovicova,David Drutovic,Petr Solc,Karen Schindler,Paula E Cohen

doi:10.1371/journal.pgen.1009327

Abstract

The Aurora protein kinases are well-established regulators of spindle building and chromosome segregation in mitotic and meiotic cells. In mouse oocytes, there is significant Aurora kinase A (AURKA) compensatory abilities when the other Aurora kinase homologs are deleted. Whether the other homologs, AURKB or AURKC can compensate for loss of AURKA is not known. Using a conditional mouse oocyte knockout model, we demonstrate that this compensation is not reciprocal because female oocyte-specific knockout mice are sterile, and their oocytes fail to complete meiosis I. In determining AURKA-specific functions, we demonstrate that its first meiotic requirement is to activate Polo-like kinase 1 at acentriolar microtubule organizing centers (aMTOCs; meiotic spindle poles). This activation induces fragmentation of the aMTOCs, a step essential for building a bipolar spindle. We also show that AURKA is required for regulating localization of TACC3, another protein required for spindle building. We conclude that AURKA has multiple functions essential to completing MI that are distinct from AURKB and AURKC.

Highlights

Haploid gametes, which are required for sexual reproduction, are generated through meiosis; a cell division that undergoes two successive rounds of chromosome segregation without an intervening round of DNA replication
In determining Aurora kinase A (AURKA)-specific functions, we demonstrate that its first meiotic requirement is to activate Polo-like kinase 1 at acentriolar microtubule organizing centers
We use a genetic approach to demonstrate that AURKA is essential for meiosis I in mouse oocytes

Summary

Introduction

Haploid gametes, which are required for sexual reproduction, are generated through meiosis; a cell division that undergoes two successive rounds of chromosome segregation without an intervening round of DNA replication. Spindle formation depends on multiple microtubule-organizing centers (MTOCs) that lack centrioles (acentriolar MTOCs; aMTOCs) but retain PCM that nucleate microtubules [7,8,9,10,11]. Perturbation of any of these steps dramatically affects the spindle structure and the interaction between microtubules and chromosomes, which can alter chromosome segregation. One result of this perturbation is that oocytes fail to complete meiosis because they activate the spindle assembly checkpoint (SAC) that monitors attachment of microtubules to kinetochores and delays anaphase onset until all kinetochores are attached to microtubules [13]

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