Terry Laura J, Wente Susan R
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
J Cell Biol. 2007 Sep 24;178(7):1121-32. doi: 10.1083/jcb.200704174. Epub 2007 Sep 17.
Trafficking of nucleic acids and large proteins through nuclear pore complexes (NPCs) requires interactions with NPC proteins that harbor FG (phenylalanine-glycine) repeat domains. Specialized transport receptors that recognize cargo and bind FG domains facilitate these interactions. Whether different transport receptors utilize preferential FG domains in intact NPCs is not fully resolved. In this study, we use a large-scale deletion strategy in Saccharomyces cerevisiae to generate a new set of more minimal pore (mmp) mutants that lack specific FG domains. A comparison of messenger RNA (mRNA) export versus protein import reveals unique subsets of mmp mutants with functional defects in specific transport receptors. Thus, multiple functionally independent NPC translocation routes exist for different transport receptors. Our global analysis of the FG domain requirements in mRNA export also finds a requirement for two NPC substructures-one on the nuclear NPC face and one in the NPC central core. These results pinpoint distinct steps in the mRNA export mechanism that regulate NPC translocation efficiency.
核酸和大蛋白通过核孔复合体（NPC）的运输需要与含有FG（苯丙氨酸-甘氨酸）重复结构域的NPC蛋白相互作用。识别货物并结合FG结构域的专门运输受体促进了这些相互作用。在完整的NPC中，不同的运输受体是否利用优先的FG结构域尚未完全解决。在本研究中，我们在酿酒酵母中使用大规模缺失策略来生成一组新的更微小孔（mmp）突变体，这些突变体缺乏特定的FG结构域。信使核糖核酸（mRNA）输出与蛋白质输入的比较揭示了在特定运输受体中具有功能缺陷的mmp突变体的独特子集。因此，不同的运输受体存在多个功能独立的NPC易位途径。我们对mRNA输出中FG结构域需求的全局分析还发现，需要两个NPC子结构——一个在核NPC面上，一个在NPC中央核心中。这些结果确定了调节NPC易位效率的mRNA输出机制中的不同步骤。
