title: Aurora kinase A drives MTOC biogenesis but does not trigger resumption of meiosis in mouse oocytes matured in vivo.
abstract: Aurora kinase A (AURKA) is an important mitotic kinase involved in the G2/M transition, centrosome maturation and separation, and spindle formation in somatic cells. We used transgenic models that specifically overexpress in mouse oocytes either wild-type (WT-AURKA) or a catalytically inactive (kinase-dead) (KD-AURKA) AURKA to gain new insights regarding the role of AURKA during oocyte maturation. AURKA activation occurs shortly after hCG administration that initiates maturation in vivo. Although AURKA activity is increased in WT-AURKA oocytes, resumption of meiosis is not observed in the absence of hCG administration. Control oocytes contain one to three microtubule organizing centers (MTOCs; centrosome equivalent) at prophase I. At the time of germinal vesicle breakdown (GVBD), the first visible marker of resumption of meiosis, the MTOC number increases. In WT-AURKA oocytes, the increase in MTOC number occurs prematurely but transiently without GVBD, whereas the increase in MTOC number does not occur in control and KD-AURKA oocytes. AURKA activation is biphasic with the initial activation not requiring CDC25B-CDK1 activity, whereas full activation, which is essential for the increase in MTOCs number, depends on CDK1 activity. AURKA activity also influences spindle length and regulates, independent of its protein kinase activity, the amount of MTOC associated with gamma-tubulin. Both WT-AURKA and KD-AURKA transgenic mice have normal fertility during first 6 mo of life. These results suggest that although AURKA is not a trigger kinase for G2/M transition in mouse oocytes, it regulates MTOC number and spindle length, and, independent of its protein kinase activity, gamma-tubulin recruitment to MTOCs.
authors: Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Libechov, Czech Republic. solc@iapg.cas.cz
authors: Petr
authors: P
authors: Solc
authors: Vladimir
authors: V
authors: Baran
authors: Alexandra
authors: A
authors: Mayer
authors: Tereza
authors: T
authors: Bohmova
authors: Gabriela
authors: G
authors: Panenkova-Havlova
authors: Adela
authors: A
authors: Saskova
authors: Richard M
authors: RM
authors: Schultz
authors: Jan
authors: J
authors: Motlik
mesh_terms: D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008540:Meiosis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022101:Microtubule-Organizing Center / Q000187:drug effects / Q000378:metabolism*; D009865:Oocytes / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D009866:Oogenesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D006063:Chorionic Gonadotropin; C576917:AURKA protein, human; C576918:Aurka protein, mouse; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases