Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
Chair of Bioanalytics, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.
PLoS Genet. 2022 Jun 6;18(6):e1009995. doi: 10.1371/journal.pgen.1009995. eCollection 2022 Jun.
Global regulation of spindle-associated proteins is crucial in oocytes due to the absence of centrosomes and their very large cytoplasmic volume, but little is known about how this is achieved beyond involvement of the Ran-importin pathway. We previously uncovered a novel regulatory mechanism in Drosophila oocytes, in which the phospho-docking protein 14-3-3 suppresses microtubule binding of Kinesin-14/Ncd away from chromosomes. Here we report systematic identification of microtubule-associated proteins regulated by 14-3-3 from Drosophila oocytes. Proteins from ovary extract were co-sedimented with microtubules in the presence or absence of a 14-3-3 inhibitor. Through quantitative mass-spectrometry, we identified proteins or complexes whose ability to bind microtubules is suppressed by 14-3-3, including the chromosomal passenger complex (CPC), the centralspindlin complex and Kinesin-14/Ncd. We showed that 14-3-3 binds to the disordered region of Borealin, and this binding is regulated differentially by two phosphorylations on Borealin. Mutations at these two phospho-sites compromised normal Borealin localisation and centromere bi-orientation in oocytes, showing that phospho-regulation of 14-3-3 binding is important for Borealin localisation and function.
纺锤体相关蛋白的全球调控对于卵母细胞至关重要,因为卵母细胞中没有中心体及其非常大的细胞质体积,但除了 Ran-importin 途径的参与外,人们对如何实现这一点知之甚少。我们之前在果蝇卵母细胞中发现了一种新的调控机制,即磷酸化 docking 蛋白 14-3-3 抑制了微管结合蛋白 Kinesin-14/Ncd 远离染色体。在这里,我们报告了系统鉴定的受 14-3-3 调控的来自果蝇卵母细胞的微管相关蛋白。在存在或不存在 14-3-3 抑制剂的情况下,卵巢提取物中的蛋白质与微管共沉淀。通过定量质谱,我们鉴定出了一些蛋白质或复合物,它们与微管的结合能力受到 14-3-3 的抑制,包括染色体乘客复合物(CPC)、中心体纺锤体复合物和 Kinesin-14/Ncd。我们表明 14-3-3 与 Borealin 的无序区域结合,而 Borealin 的两个磷酸化位点对这种结合的调节是不同的。这两个磷酸化位点的突变会破坏卵母细胞中 Borealin 的正常定位和着丝粒的双定向,表明 14-3-3 结合的磷酸化调节对于 Borealin 的定位和功能很重要。