Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
Laboratory of Gene Expression Regulation in Development, Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
PLoS Genet. 2019 Mar 13;15(3):e1008012. doi: 10.1371/journal.pgen.1008012. eCollection 2019 Mar.
orb is a founding member of the CPEB family of translational regulators and is required at multiple steps during Drosophila oogenesis. Previous studies showed that orb is required during mid-oogenesis for the translation of the posterior/germline determinant oskar mRNA and the dorsal-ventral determinant gurken mRNA. Here, we report that orb also functions upstream of these axes determinants in the polarization of the microtubule network (MT). Prior to oskar and gurken translational activation, the oocyte MT network is repolarized. The MT organizing center at the oocyte posterior is disassembled, and a new MT network is established at the oocyte anterior. Repolarization depends upon cross-regulatory interactions between anterior (apical) and posterior (basal) Par proteins. We show that repolarization of the oocyte also requires orb and that orb is needed for the proper functioning of the Par proteins. orb interacts genetically with aPKC and cdc42 and in egg chambers compromised for orb activity, Par-1 and aPKC protein and aPKC mRNA are mislocalized. Moreover, like cdc42-, the defects in Par protein localization appear to be connected to abnormalities in the cortical actin cytoskeleton. These abnormalities also disrupt the localization of the spectraplakin Shot and the microtubule minus-end binding protein Patronin. These two proteins play a critical role in the repolarization of the MT network.
orb 是 CPEB 家族翻译调节因子的创始成员，在果蝇卵子发生的多个步骤中都需要它。以前的研究表明，orb 在卵子发生的中期对于后部/生殖细胞决定因子 Oskar mRNA 和背-腹决定因子 Gurken mRNA 的翻译是必需的。在这里，我们报告 orb 也在前部/后部轴决定因素的极化中在微管网络（MT）的上游起作用。在 Oskar 和 Gurken 翻译激活之前，卵母细胞的 MT 网络被重新极化。卵母细胞后部的 MT 组织中心被分解，并且在卵母细胞的前部建立了新的 MT 网络。重新极化取决于前（顶端）和后（基底）Par 蛋白之间的交叉调节相互作用。我们表明，卵母细胞的重新极化也需要 orb，并且 orb 对于 Par 蛋白的正常功能是必需的。orb 在遗传上与 aPKC 和 cdc42 相互作用，并且在 orb 活性受损的卵囊中，Par-1 和 aPKC 蛋白和 aPKC mRNA 被错误定位。此外，与 cdc42 一样，Par 蛋白定位的缺陷似乎与皮质肌动球蛋白细胞骨架的异常有关。这些异常也破坏了 spectraplakin Shot 和微管末端结合蛋白 Patronin 的定位。这两种蛋白在 MT 网络的重新极化中起着关键作用。
