Galy Vincent, Mattaj Iain W, Askjaer Peter
European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Mol Biol Cell. 2003 Dec;14(12):5104-15. doi: 10.1091/mbc.e03-04-0237. Epub 2003 Aug 22.
Nuclear pore complexes (NPCs) span the nuclear envelope and mediate communication between the nucleus and the cytoplasm. To obtain insight into the structure and function of NPCs of multicellular organisms, we have initiated an extensive analysis of Caenorhabditis elegans nucleoporins. Of 20 assigned C. elegans nucleoporin genes, 17 were found to be essential for embryonic development either alone or in combination. In several cases, depletion of nucleoporins by RNAi caused severe defects in nuclear appearance. More specifically, the C. elegans homologs of vertebrate Nup93 and Nup205 were each found to be required for normal NPC distribution in the nuclear envelope in vivo. Depletion of Nup93 or Nup205 caused a failure in nuclear exclusion of nonnuclear macromolecules of approximately 70 kDa without preventing active nuclear protein import or the assembly of the nuclear envelope. The defects in NPC exclusion were accompanied by abnormal chromatin condensation and early embryonic arrest. Thus, the contribution to NPC structure of Nup93 and Nup205 is essential for establishment of normal NPC function and for cell viability.
核孔复合体(NPCs)跨越核膜,介导细胞核与细胞质之间的通讯。为深入了解多细胞生物NPCs的结构和功能,我们已着手对秀丽隐杆线虫核孔蛋白进行广泛分析。在已确定的20个秀丽隐杆线虫核孔蛋白基因中,发现17个单独或组合起来对胚胎发育至关重要。在几种情况下,RNA干扰导致核孔蛋白缺失会引起细胞核外观的严重缺陷。更具体地说,已发现脊椎动物Nup93和Nup205的秀丽隐杆线虫同源物各自对于体内核膜中正常NPC分布是必需的。Nup93或Nup205缺失导致约70 kDa的非核大分子无法被细胞核排除,同时并不妨碍活性核蛋白的导入或核膜的组装。NPC排除缺陷伴随着染色质异常凝聚和早期胚胎停滞。因此,Nup93和Nup205对NPC结构的贡献对于正常NPC功能的建立和细胞活力至关重要。