Makhnevych Taras, Lusk C Patrick, Anderson Andrea M, Aitchison John D, Wozniak Richard W
Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
Cell. 2003 Dec 26;115(7):813-23. doi: 10.1016/s0092-8674(03)00986-3.
Eukaryotic cells have developed mechanisms for regulating the nuclear transport of macromolecules that control various cellular events including movement through defined stages of the cell cycle. In yeast cells, where the nuclear envelope remains intact throughout the cell cycle, these transport regulatory mechanisms must also function during mitosis. We have uncovered a mechanism for regulating transport that is controlled by M phase specific molecular rearrangements in the nuclear pore complex (NPC). These changes allow a transport inhibitory nucleoporin, Nup53p, to bind the karyopherin Kap121p specifically during mitosis, slowing its movement through the NPC and inducing cargo release. Yeast strains that possess defects in the function of Kap121p or the fidelity of the inhibitory pathway are delayed in mitosis. We propose that fluctuations in Kap121p transport mediated by the NPC contribute to controlling the subcellular distribution of molecules that direct progression through mitosis.
真核细胞已经形成了调节大分子核运输的机制,这些机制控制着各种细胞活动,包括细胞周期特定阶段的进程。在酵母细胞中,核膜在整个细胞周期中保持完整,这些运输调节机制在有丝分裂期间也必须发挥作用。我们发现了一种由核孔复合体(NPC)中M期特异性分子重排控制的运输调节机制。这些变化使得一种运输抑制性核孔蛋白Nup53p在有丝分裂期间特异性地结合核转运蛋白Kap121p,减缓其通过NPC的移动并诱导货物释放。在Kap121p功能或抑制途径保真度方面存在缺陷的酵母菌株在有丝分裂中会延迟。我们提出,由NPC介导的Kap121p运输波动有助于控制指导有丝分裂进程的分子的亚细胞分布。