Nup358, a nucleoporin, functions as a key determinant of the nuclear pore complex structure remodeling during skeletal myogenesis
Nup358, a nucleoporin, functions as a key determinant of the nuclear pore complex structure remodeling during skeletal myogenesis
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DOI：
10.1111/j.1742-4658.2010.07982.x
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发表时间：
2011-02-01
期刊：
影响因子：
5.4
通讯作者：
Yoneda, Yoshihiro
中科院分区：
文献类型：
--
作者：
Asally, Munehiro;Yasuda, Yoshinari;Yoneda, Yoshihiro
核孔复合物（NPC）是分子穿过核膜运输的唯一通道。NPC不仅仅是一个静态的核质转运门;核孔蛋白的功能分析揭示了NPC在各种细胞功能中的动态特征，如有丝分裂纺锤体形成和蛋白质修饰。然而，目前尚不清楚NPC是否在细胞分化等生物学过程中发生动态变化。在本研究中，我们评估了几种核孔蛋白表达水平的变化，并表明在C2 C12细胞肌肉分化过程中，单个NPC内Nup 358/RanBP 2的量增加。使用原子力显微镜，我们证明成肌细胞和肌管NPC的细胞质表面之间的结构差异和Nup 358的拷贝数和NPC结构之间的相关性。此外，小干扰RNA介导的成肌细胞中NUP 358的耗竭抑制肌管形成而不影响细胞活力，表明NUP 358在肌发生中起作用。这些发现表明NPC在肌细胞分化过程中经历动态重塑，并且Nup 358显著参与重塑过程。
The nuclear pore complex (NPC) is the only gateway for molecular trafficking across the nuclear envelope. The NPC is not merely a static nuclear-cytoplasmic transport gate; the functional analysis of nucleoporins has revealed dynamic features of the NPC in various cellular functions, such as mitotic spindle formation and protein modification. However, it is not known whether the NPC undergoes dynamic changes during biological processes such as cell differentiation. In the present study, we evaluate changes in the expression levels of several nucleoporins and show that the amount of Nup358/RanBP2 within individual NPCs increases during muscle differentiation in C2C12 cells. Using atomic force microscopy, we demonstrate structural differences between the cytoplasmic surfaces of myoblast and myotube NPCs and a correlation between the copy number of Nup358 and the NPC structure. Furthermore, small interfering RNA-mediated depletion of Nup358 in myoblasts suppresses myotube formation without affecting cell viability, suggesting that NUP358 plays a role in myogenesis. These findings indicate that the NPC undergoes dynamic remodeling during muscle cell differentiation and that Nup358 is prominently involved in the remodeling process.