Nuclear Pores Regulate Muscle Development and Maintenance by Assembling a Localized Mef2C Complex.
Nuclear Pores Regulate Muscle Development and Maintenance by Assembling a Localized Mef2C Complex.
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DOI：
10.1016/j.devcel.2017.05.007
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发表时间：
2017-06-05
影响因子：
11.8
通讯作者：
D'Angelo MA
中科院分区：
文献类型：
--
作者：
Raices M;Bukata L;Sakuma S;Borlido J;Hernandez LS;Hart DO;D'Angelo MA
核孔复合物（NPCs）是连接细胞核和细胞质的多蛋白通道。npc已被证明具有组织特异性组成，这表明它们的功能可以特殊化。然而，鼻咽癌成分变化的生理作用及其对细胞过程的影响尚不清楚。本研究表明，在成肌细胞分化过程中，NPCs中加入Nup210核孔蛋白会导致Mef2C转录复合体的组装，而Mef2C转录复合体是有效表达肌肉结构基因和microrna所必需的。我们发现这种npc定位的复合体对肌肉生长、肌纤维成熟和肌肉细胞存活至关重要，其活性的改变会导致肌肉变性。我们的研究结果表明，NPCs通过作为促进组织特异性转录复合物的局部组装的支架来调节功能基因群的活性，并表明核孔组成的变化如何被利用来调节核周围的基因表达。
Nuclear pore complexes (NPCs) are multiprotein channels connecting the nucleus with the cytoplasm. NPCs have been shown to have tissue-specific composition, suggesting that their function can be specialized. However, the physiological roles of NPC composition changes and their impacts on cellular processes remain unclear. Here we show that the addition of the Nup210 nucleoporin to NPCs during myoblast differentiation results in assembly of an Mef2C transcriptional complex required for efficient expression of muscle structural genes and microRNAs. We show that this NPC-localized complex is essential for muscle growth, myofiber maturation, and muscle cell survival and that alterations in its activity result in muscle degeneration. Our findings suggest that NPCs regulate the activity of functional gene groups by acting as scaffolds that promote the local assembly of tissue-specific transcription complexes and show how nuclear pore composition changes can be exploited to regulate gene expression at the nuclear periphery.
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