Bora regulates meiotic spindle assembly and cell cycle during mouse oocyte meiosis

Abstract

Bora is the binding partner of Aurora A, which is required for its activation and phosphorylation of Polo like kinase 1 (Plk1), and is involved in the spindle assembly and progress of the cell cycle during mitosis. In this study, we examined the expression, localization, and function of Bora during mouse oocyte meiosis. The expression level of Bora was increased during oocyte meiotic maturation, with an elevated level at metaphase. Immunofluorescence analysis showed that Bora was concentrated as a dot shortly after germinal vesicle breakdown (GVBD), associating first with the surrounding chromosomes and then with the spindle throughout oocyte meiotic maturation. Further experiments confirmed that Bora co-localized with α-tubulin at prometaphase/metaphase, but dissociated from α-tubulin at anaphase/telophase. In metaphase-II-arrested oocytes, Bora was evenly distributed in the cytoplasm after treatment with a microtubule-depolymerizing agent, or recruited to the spindle after treatment with a microtubule-polymerizing agent, indicating that Bora was physically connected to the meiotic spindle and α-tubulin at metaphase. Furthermore, inhibition or depletion of Bora by either anti-Bora antibody or Bora siRNA microinjection significantly reduced the rates of GVBD and inhibited first polar body extrusion; caused morphologically defective spindles and misaligned chromosomes; arrested maturing oocytes at prometaphase/metaphase-I stage, or left oocytes and their first polar bodies with severely misaligned chromosomes and defective spindles; and/or caused the disappearance of Aurora A and Plk1 at the spindle. These results indicated that Bora acts as a critical regulator of Aurora A and Plk1, and is involved in microtubule organization during oocyte meiosis.

Phosphorylation-mediated stabilization of Bora in mitosis coordinates Plx1/Plk1 and Cdk1 oscillations

“…We thus conclude that, similar to what happens in somatic cells and mouse oocytes, 26 Bora is present in CSF extract, and its degradation is mediated by Cdk1, Plx1, and the SCF β-TrCP . However, in contrast to somatic cells, degradation of Bora in CSF extracts apparently requires an additional step triggered by calcium.…”

“…Bora has recently been identified in mouse oocytes; 26 however, we wondered whether Xenopus oocytes also express endogenous Bora. According to unigene transcript data (http://www.ncbi.…”

Bcl2l10, a new Tpx2 binding partner, is a master regulator of Aurora kinase A in mouse oocytes

“…28 In addition, Bora, known as a binding partner of Aurka, regulates the precise localization of Aurka and Plk1. 29 The protein expression of Bora was significantly reduced, and the levels of Plk1, phosphorylated Tpx2 also showed a decreasing tendency following Bcl2l10 RNAi (Fig. 6A and B).…”

“…We expected to identify a new protein that phosphorylates Plk1 and maintains Plk1 phosphorylation in Bcl2l10 RNAi-treated oocytes. Although the expression patterns and functions of these genes in oocyte meiosis were in many ways unlike those in mitosis, 15,29,39,44 it could be concluded that Bcl2l10 is strongly engaged as a part of the cascade of the BoraPlk1-Tpx2-Aurka pathway for regulating meiosis.…”

Specialize and Divide (Twice): Functions of Three Aurora Kinase Homologs in Mammalian Oocyte Meiotic Maturation

“…Inspection of these arrested embryos revealed loss of AURKA at spindles and defective microtubule nucleation. In addition to TPX2, Bora , another AURKA binding partner, is critical for the localization and activation of AURKA at spindle poles in mouse oocytes [35]. In wild-type oocytes Bora co-localizes with AURKA at spindle poles and depletion of Bora using siRNA disrupts AURKA localization and results in abnormal spindle morphologies and misaligned chromosomes at Met I.…”