PP2A regulates kinetochore-microtubule attachment during meiosis I in oocyte.
Studies using in vitro cultured oocytes have indicated that the protein phosphatase 2A (PP2A), a major serine/threonine protein phosphatase, participates in multiple steps of meiosis. Details of oocyte maturation regulation by PP2A remain unclear and an in vivo model can provide more convincing information. Here, we inactivated PP2A by mutating genes encoding for its catalytic subunits (PP2Acs) in mouse oocytes. We found that eliminating both PP2Acs caused female infertility. Oocytes lacking PP2Acs failed to complete 1(st) meiotic division due to chromosome misalignment and abnormal spindle assembly. In mitosis, PP2A counteracts Aurora kinase B/C (AurkB/C) to facilitate correct kinetochore-microtubule (KT-MT) attachment. In meiosis I in oocyte, we found that PP2Ac deficiency destabilized KT-MT attachments. Chemical inhibition of AurkB/C in PP2Ac-null oocytes partly restored the formation of lateral/merotelic KT-MT attachments but not correct KT-MT attachments. Taken together, our findings demonstrate that PP2Acs are essential for chromosome alignments and regulate the formation of correct KT-MT attachments in meiosis I in oocytes.
a State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Collaborative Innovation Center of Genetics and Development, Nanjing University , Nanjing , China.
An
A
Tang
a State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Collaborative Innovation Center of Genetics and Development, Nanjing University , Nanjing , China.
Peiliang
P
Shi
a State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Collaborative Innovation Center of Genetics and Development, Nanjing University , Nanjing , China.
Anying
A
Song
a State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Collaborative Innovation Center of Genetics and Development, Nanjing University , Nanjing , China.
Dayuan
D
Zou
b State Key Laboratory of Food Science and Technology, Jiangnan University , Wuxi , China.
Yue
Y
Zhou
c Neurobiology Department , University of Massachusetts Medical School , Worcester , MA , USA.
Pengyu
P
Gu
d College of Animal Science & Technology, Nanjing Agricultural University , Nanjing , China.
Zan
Z
Huang
a State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Collaborative Innovation Center of Genetics and Development, Nanjing University , Nanjing , China.
Qinghua
Q
Wang
a State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Collaborative Innovation Center of Genetics and Development, Nanjing University , Nanjing , China.
Zhaoyu
Z
Lin
a State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Collaborative Innovation Center of Genetics and Development, Nanjing University , Nanjing , China.
Xiang
X
Gao
D000595:Amino Acid Sequence; D000818:Animals; D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism; D064108:Aurora Kinase C / Q000235:genetics / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007247:Infertility, Female / Q000235:genetics / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism* / Q000648:ultrastructure; D008540:Meiosis; D051379:Mice; D008822:Mice, Transgenic; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008938:Mitosis; D009865:Oocytes / Q000378:metabolism* / Q000648:ultrastructure; D061251:Primary Cell Culture; D054648:Protein Phosphatase 2 / Q000235:genetics* / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure
D021122:Protein Subunits; C576921:AURKB protein, human; C576927:AURKC protein, human; D064107:Aurora Kinase B; D064108:Aurora Kinase C; D054648:Protein Phosphatase 2
KT-MT attachment; PP2A; fertility; meiosis; oocyte