NDC1: a crucial membrane-integral nucleoporin of metazoan nuclear pore complexes.

NDC1: a crucial membrane-integral nucleoporin of metazoan nuclear pore complexes.
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DOI:
10.1083/jcb.200601001
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发表时间:
2006-05-22
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Görlich D
Görlich D
中科院分区:
其他
文献类型:
--
作者:
Stavru F;Hülsmann BB;Spang A;Hartmann E;Cordes VC;Görlich D

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在此之前,POM 121和gp 210是脊椎动物中唯一已知的膜整合核孔蛋白(NUP),因此也是核膜内核孔复合物(NPC)的唯一候选锚。在一项附带的研究中(见Stavru et al. on p. of this issue),我们提供的证据表明NPC可以独立于POM 121和gp 210存在,我们预测脊椎动物NPC含有额外的膜整合成分。我们确定这样一个额外的膜蛋白在哺乳动物,青蛙,昆虫和线虫的NPC作为直系同源酵母Ndc 1 p/Cut 11 p。人NDC 1(hNDC 1)可能具有六个跨膜片段,并且其位于核孔壁。从人HeLa细胞中消耗hNDC 1干扰苯丙氨酸-甘氨酸重复Nups组装成NPC。秀丽隐杆线虫中NDC 1功能的丧失也导致严重的NPC缺陷和非常高的幼虫和胚胎死亡率。然而,它最终并不致命。相反,纯合的NDC 1缺陷型蠕虫可以繁殖。这表明,没有一个膜整合的Nup是NPC组装普遍必需的,并表明NPC生物发生是一个非常容错的过程。
POM121 and gp210 were, until this point, the only known membrane-integral nucleoporins (Nups) of vertebrates and, thus, the only candidate anchors for nuclear pore complexes (NPCs) within the nuclear membrane. In an accompanying study (see Stavru et al. on p. of this issue), we provided evidence that NPCs can exist independently of POM121 and gp210, and we predicted that vertebrate NPCs contain additional membrane-integral constituents. We identify such an additional membrane protein in the NPCs of mammals, frogs, insects, and nematodes as the orthologue to yeast Ndc1p/Cut11p. Human NDC1 (hNDC1) likely possesses six transmembrane segments, and it is located at the nuclear pore wall. Depletion of hNDC1 from human HeLa cells interferes with the assembly of phenylalanine-glycine repeat Nups into NPCs. The loss of NDC1 function in Caenorhabditis elegans also causes severe NPC defects and very high larval and embryonic mortality. However, it is not ultimately lethal. Instead, homozygous NDC1-deficient worms can be propagated. This indicates that none of the membrane-integral Nups is universally essential for NPC assembly, and suggests that NPC biogenesis is an extremely fault-tolerant process.
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