Aurora kinase A is essential for meiosis in mouse oocytes

0542519 - ÚŽFG 2022 RIV US eng J - Článek v odborném periodiku
Blengini, C. S. - Ibrahimian, P. - Vaškovičová, Michaela - Drutovič, Dávid - Šolc, Petr - Schindler, K.
Aurora kinase A is essential for meiosis in mouse oocytes.
PLoS Genetics. Roč. 17, č. 4 (2021), č. článku e1009327. ISSN 1553-7404. E-ISSN 1553-7404
Grant CEP: GA MŠMT(CZ) LTAUSA17097; GA MŠMT(CZ) LO1609
Institucionální podpora: RVO:67985904
Klíčová slova: Aurora kinase A * mouse oocytes
Obor OECD: Developmental biology
Impakt faktor: 6.020, rok: 2021
Způsob publikování: Open access
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009327

Female gametes, oocytes, are uniquely prone to chromosome segregation errors in meiosis I that are associated with early miscarriages. The Aurora protein kinases are essential to control chromosome segregation in all cell types. During mitosis, Aurora kinase A (AURKA) regulates the building of the spindle, the machinery responsible for pulling chromosomes apart. Here, we use a genetic approach to demonstrate that AURKA is essential for meiosis I in mouse oocytes. AURKA is required at multiple steps in meiosis I, first to trigger fragmentation of protein structures that make up the two ends of the meiotic spindle and later to regulate the proper localization of TACC3 to build a normal bipolar spindle. These findings are the first demonstration of distinct Aurora kinase function that cannot be compensated for by the other two homologs. Therefore, this mouse model is excellent tool for pinpointing specific Aurora kinase functions and identifying AURKA target proteins critical for chromosome segregation in meiosis I.
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.
Trvalý link: http://hdl.handle.net/11104/0319914