Stavru Fabrizia, Nautrup-Pedersen Gitte, Cordes Volker C, Görlich Dirk
Zentrum für Molekulare Biologie der Universität Heidelberg, D-69120 Heidelberg, Germany.
J Cell Biol. 2006 May 22;173(4):477-83. doi: 10.1083/jcb.200601002. Epub 2006 May 15.
So far, POM121 and gp210 are the only known anchoring sites of vertebrate nuclear pore complexes (NPCs) within the lipid bilayer of the nuclear envelope (NE) and, thus, are excellent candidates for initiating the NPC assembly process. Indeed, we demonstrate that POM121 can recruit several nucleoporins, such as Nup62 or Nup358, to ectopic assembly sites. It thus appears to act as a nucleation site for the assembly of NPC substructures. Nonetheless, we observed functional NPCs and intact NEs in severely POM121-depleted cells. Double knockdowns of gp210 and POM121 in HeLa cells, as well as depletion of POM121 from human fibroblasts, which do not express gp210, further suggest that NPCs can assemble or at least persist in a POM121- and gp210-free form. This points to extensive redundancies in protein-protein interactions within NPCs and suggests that vertebrate NPCs contain additional membrane-integral nucleoporins for anchorage within the lipid bilayer of the NE. In Stavru et al., we describe such an additional transmembrane nucleoporin as the metazoan orthologue of yeast Ndc1p.
到目前为止，POM121和gp210是脊椎动物核孔复合体（NPC）在核膜（NE）脂质双层中仅有的已知锚定位点，因此，它们是启动NPC组装过程的极佳候选者。事实上，我们证明POM121可以将几种核孔蛋白，如Nup62或Nup358，招募到异位组装位点。因此，它似乎充当了NPC亚结构组装的成核位点。尽管如此，我们在严重缺乏POM121的细胞中观察到了功能性NPC和完整的NE。在HeLa细胞中对gp210和POM121进行双敲低，以及在不表达gp210的人成纤维细胞中耗尽POM121，进一步表明NPC可以以无POM121和gp210的形式组装或至少持续存在。这表明NPC内蛋白质-蛋白质相互作用存在广泛的冗余，并表明脊椎动物NPC含有额外的膜整合核孔蛋白，用于在NE的脂质双层中锚定。在Stavru等人的研究中，我们将这样一种额外的跨膜核孔蛋白描述为酵母Ndc1p的后生动物直系同源物。
