Genetic interactions between the Aurora kinases reveal new requirements for AURKB and AURKC during oocyte meiosis
| Autor: | Marcos Malumbres, Alexandra L. Nguyen, Berta N. Vazquez, Karen Schindler, David Drutovic, Warif El Yakoubi, Amanda S. Gentilello, Petr Solc |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Biology General Biochemistry Genetics and Molecular Biology Article Chromosome segregation 03 medical and health sciences Mice Aurora kinase Meiosis Chromosome Segregation Homologous chromosome Animals Aurora Kinase B Aurora Kinase C Mitosis Aurora Kinase A Female meiosis I Aneuploidy Cell biology Spindle checkpoint 030104 developmental biology Fertility Oocytes Female General Agricultural and Biological Sciences Cytokinesis |
| Popis: | SUMMARY: 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, 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], while 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. ETOC BLURB: Nguyen et al. describe oocyte-specific functions for the three Aurora protein kinases during meiosis. The authors show, for the first time, negative inter-kinase regulation between the family members to control the localized activity of one another, and that these interactions are critical for spindle integrity and gamete euploidy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|