The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Dev Cell. 2013 Aug 12;26(3):303-14. doi: 10.1016/j.devcel.2013.06.011.
Translation of oskar messenger RNA (mRNA) is activated at the posterior of the Drosophila oocyte, producing Long Oskar, which anchors the RNA, and Short Oskar, which nucleates the pole plasm, containing the posterior and germline determinants. Here, we show that Oskar is phosphorylated by Par-1 and GSK-3/Shaggy to create a phosphodegron that recruits the SCF(-Slimb) ubiquitin ligase, which targets Short Oskar for degradation. Phosphorylation site mutations cause Oskar overaccumulation, leading to an increase in pole cell number and embryonic patterning defects. Furthermore, the nonphosphorylatable mutant produces bicaudal embryos when oskar mRNA is mislocalized. Thus, the Par-1/GSK-3/Slimb pathway plays important roles in limiting the amount of pole plasm posteriorly and in degrading any mislocalized Oskar that results from leaky translational repression. These results reveal that Par-1 controls the timing of pole plasm assembly by promoting the localization of oskar mRNA but inhibiting the accumulation of Short Oskar protein.
果蝇卵子后极的 Oskar 信使 RNA (mRNA) 翻译被激活，产生长 Oskar，它锚定 RNA，短 Oskar 则起始极质，包含后极和生殖系决定因素。在这里，我们表明 Oskar 被 Par-1 和 GSK-3/Shaggy 磷酸化，产生一个招募 SCF(-Slimb)泛素连接酶的磷酸化降解序列，该酶将短 Oskar 靶向降解。磷酸化位点突变导致 Oskar 过度积累，导致极细胞数量增加和胚胎模式缺陷。此外，当 Oskar mRNA 定位错误时，非磷酸化突变体会产生双头胚胎。因此，Par-1/GSK-3/Slimb 途径在限制极质后端的量和降解任何由于翻译抑制泄漏而导致的错误定位的 Oskar 方面发挥着重要作用。这些结果表明，Par-1 通过促进 Oskar mRNA 的定位但抑制短 Oskar 蛋白的积累来控制极质组装的时间。
