Expression and characterization of three Aurora kinase C splice variants found in human oocytes

Jessica E. Fellmeth, Derek Gordon, Christian E. Robins, Richard T. Scott, Nathan R. Treff, Karen Schindler

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Chromosome segregation is an extensively choreographed process yet errors still occur frequently in female meiosis, leading to implantation failure, miscarriage or offspring with developmental disorders. Aurora kinase C (AURKC) is a component of the chromosome passenger complex and is highly expressed in gametes. Studies in mouse oocytes indicate that AURKC is required to regulate chromosome segregation during meiosis I; however, little is known about the functional significance of AURKC in human oocytes. Three splice variants of AURKC exist in testis tissue.To determine which splice variants human oocytes express,weperformed quantitative real-timePCRusing single oocytes and found expression of all three variants. To evaluate the functional differences between the variants, we created green fluorescent protein-tagged constructs of each variant to express in oocytes from Aurkc2/2 mice. By quantifying metaphase chromosome alignment, cell cycle progression, phosphorylation of INCENP and microtubule attachments to kinetochores, we found that AURKC_v1 was the most capable of the variants at supporting metaphase I chromosome segregation.AURKC_v3localized to chromosomes properly and supported cell cycle progression to metaphase II, but its inability to correct erroneous microtubule attachments to kinetochores meant that chromosome segregationwas not as accurate compared with the other two variants. Finally, whenweexpressed the three variants simultaneously, error correction wasmore robust than when theywere expressed on theirown. Therefore, oocytes express three variants ofAURKCthat are not functionally equivalent in supporting meiosis, but fully complement meiosis when expressed simultaneously.

Original languageEnglish (US)
Pages (from-to)633-644
Number of pages12
JournalMolecular human reproduction
Volume21
Issue number8
DOIs
StatePublished - Mar 10 2015

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Embryology
  • Molecular Biology
  • Genetics
  • Obstetrics and Gynecology
  • Developmental Biology
  • Cell Biology

Keywords

  • Aurora kinase C
  • Female fertility
  • Meiosis
  • Oocyte maturation

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