Aurora-C kinase deficiency causes cytokinesis failure in meiosis I and production of large polyploid oocytes in mice.
We previously isolated Aurora-C/Aie1 in a screen for kinases expressed in mouse sperm and eggs. Here, we show the localization of endogenous Aurora-C and examine its roles during female mouse meiosis. Aurora-C was detected at the centromeres and along the chromosome arms in prometaphase I-metaphase I and was concentrated at centromeres at metaphase II, in which Aurora-C also was phosphorylated at Thr171. During the anaphase I-telophase I transition, Aurora-C was dephosphorylated and relocalized to the midzone and midbody. Microinjection of the kinase-deficient Aurora-C (AurC-KD) mRNA into mouse oocytes significantly inhibited Aurora-C activity and caused multiple defects, including chromosome misalignment, abnormal kinetochore-microtubule attachment, premature chromosome segregation, and cytokinesis failure in meiosis I. Furthermore, AurC-KD reduced Aurora-C and histone H3 phosphorylation and inhibited kinetochore localization of Bub1 and BubR1. Similar effects also were observed in the oocytes injected with INCNEP-delIN mRNAs, in which the Aurora-C binding motif was removed. The most dramatic effect observed in AurC-KD-injected oocytes is cytokinesis failure in meiosis I, resulting in producing large polyploid oocytes, a pattern similar to Aurora-C deficiency human spermatozoa. Surprisingly, we detected no Aurora-B protein in mouse oocytes. We propose that Aurora-C, but not Aurora-B, plays essential roles in female mouse meiosis.
Yang
Kuo-Tai
KT
Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 115, Taiwan.
Li
Shu-Kuei
SK
Chang
Chih-Chieh
CC
Tang
Chieh-Ju C
CJ
Lin
Yi-Nan
YN
Lee
Sheng-Chung
SC
Tang
Tang K
TK
D000818:Animals; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation; D033481:Chromosomes, Mammalian / Q000378:metabolism; D048749:Cytokinesis; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009865:Oocytes / Q000166:cytology* / Q000201:enzymology*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011123:Polyploidy; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000378:metabolism*; D021381:Protein Transport
C584278:Bub1b protein, mouse; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; C083767:INCENP protein, human; D049452:Green Fluorescent Proteins; D010768:Phosphoserine; C576921:AURKB protein, human; C576927:AURKC protein, human; C576924:Aurkb protein, mouse; C576928:Aurkc protein, mouse; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D064127:Aurora Kinases; C584277:BUB1 protein, human; C584281:Bub1 protein, mouse; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases