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合子 NUP107 蛋白缺失导致斑马鱼胚胎咽弓骨骼缺失和其他组织缺陷,并影响核孔功能。

Loss of zygotic NUP107 protein causes missing of pharyngeal skeleton and other tissue defects with impaired nuclear pore function in zebrafish embryos.

机构信息

State Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.

出版信息

J Biol Chem. 2012 Nov 2;287(45):38254-64. doi: 10.1074/jbc.M112.408997. Epub 2012 Sep 10.

Abstract

The Nup107-160 multiprotein subcomplex is essential for the assembly of nuclear pore complexes. The developmental functions of individual constituents of this subcomplex in vertebrates remain elusive. In particular, it is unknown whether Nup107 plays an important role in development of vertebrate embryos. Zebrafish nup107 is maternally expressed and its zygotic expression becomes prominent in the head region and the intestine from 24 h postfertilization (hpf) onward. In this study, we generate a zebrafish mutant line, nup107(tsu068Gt), in which the nup107 locus is disrupted by an insertion of Tol2 transposon element in the first intron and as a result it fails to produce normal transcripts. Homozygous nup107(tsu068Gt) mutant embryos exhibit tissue-specific defects after 3 days postfertilization (dpf), including loss of the pharyngeal skeletons, degeneration of the intestine, absence of the swim bladder, and smaller eyes. These mutants die at 5-6 days. Extensive apoptosis occurs in the affected tissues, which is partially dependent on p53 apoptotic pathways. In cells of the defective tissues, FG-repeat nucleoporins are disturbed and nuclear pore number is reduced, leading to impaired translocation of mRNAs from the nucleus to the cytoplasm. Our findings shed new light on developmental function of Nup107 in vertebrates.

摘要

Nup107-160 多蛋白亚基复合物对于核孔复合物的组装是必不可少的。该亚基复合物中各个成分在脊椎动物中的发育功能仍然难以捉摸。特别是,尚不清楚 Nup107 是否在脊椎动物胚胎发育中发挥重要作用。斑马鱼 nup107 呈母源表达,其合子表达在受精后 24 小时(hpf)开始在头部区域和肠道中变得明显。在这项研究中,我们生成了一种斑马鱼突变系 nup107(tsu068Gt),其中 nup107 基因座被 Tol2 转座子元件插入到第一个内含子中,从而无法产生正常的转录物。纯合 nup107(tsu068Gt)突变体胚胎在受精后 3 天(dpf)后表现出组织特异性缺陷,包括咽骨缺失、肠道退化、鳔缺失和眼睛变小。这些突变体在 5-6 天死亡。受影响的组织中发生广泛的细胞凋亡,部分依赖于 p53 凋亡途径。在有缺陷的组织细胞中,FG-重复核孔蛋白受到干扰,核孔数量减少,导致从细胞核到细胞质的 mRNA 转位受损。我们的发现为 Nup107 在脊椎动物中的发育功能提供了新的认识。

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