PP2A regulates kinetochore-microtubule attachment during meiosis I in oocyte
Open accessAbstract
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.
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These defects correlated with increased phosphorylation of Aurora kinase substrates hKNL1 (Ser24) and Histone H3 (Ser10), and could be partially rescued by hesperadin.
“These defects correlated with increased phosphorylation of the Aurora kinase substrates, hKNL1 (Ser24) and Histone H3 (Ser10), and could be partially rescued by the pharmacologic Aurora kinase B/C inhibitor, hesperadin.”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [28]
Only double Ppp2ca × Ppp2cb knockout completely compromised female fertility.
“On the other hand, conditional KO of either Ppp2ca or Ppp2cb in oocytes at primary follicular stages resulted in normal female fertility [28]; only upon double Ppp2ca × Ppp2cb KO, female fertility was completely compromised [28].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [28]
In double knockout mice, ovary morphology and ovulation appeared normal, but defective oocytes were observed with lack of the first meiotic division, chromosome congression, alignment and segregation defects, and an abnormal acentrosomal spindle in meiosis-I.
“While in these mice, ovary morphology and ovulation appeared normal, defective oocytes were observed, characterized by a lack of the first meiotic division, chromosome congression, alignment and segregation defects, and formation of an abnormal acentrosomal spindle in meiosis-I.”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [28]
Conditional knockout of either Ppp2ca or Ppp2cb in oocytes at primary follicular stages resulted in normal female fertility.
“On the other hand, conditional KO of either Ppp2ca or Ppp2cb in oocytes at primary follicular stages resulted in normal female fertility [28]; only upon double Ppp2ca × Ppp2cb KO, female fertility was completely compromised [28].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [28]
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Physiologic functions of PP2A: Lessons from genetically modified mice
Reynhout, S., & Janssens, V. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.07.010 · Cited by 124 · see citing works
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- Authors
- Tang, A., Shi, P., Song, A., Zou, D., Zhou, Y., Gu, P., Huang, Z., Wang, Q., Lin, Z., & Gao, X.
- Affiliations
- Model Animal Research Center (CN)
- Jiangnan University (CN)
- University of Massachusetts Chan Medical School (US)
- Nanjing Agricultural University (CN)
- Corresponding author
- Lin, Zhaoyu
- Gao, Xiang
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2016-05-13
- Volume
- 15
- Issue
- 11
- Pages
- 1450-1461
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- PMC
- PMC4934050
- OpenAlex
- W2338403687
- Cited by
- 29
- References
- 47
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 5 · 2016: 1
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (2014BAI02B01, 31301217, 2015BAI08B02, 11KJB180010)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- protein phosphatase 2A, PP2A catalytic subunit, kinetochore-microtubule attachment, meiosis I, oocyte maturation, chromosome alignment, spindle assembly, female infertility, merotelic attachment, chromosome segregation
- MeSH terms
- Amino Acid Sequence, Animals, Female, Infertility, Female, Meiosis, Mice, Transgenic, Microtubules, Mitosis, Spindle Apparatus, Oocytes, Signal Transduction, Kinetochores, Gene Expression Regulation, Developmental, Protein Subunits, Chromosomes, Mammalian, Mice, Protein Phosphatase 2, Primary Cell Culture, Aurora Kinase B, Aurora Kinase C
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