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The nuclear envelope protein Nesprin-2 has roles in cell proliferation and differentiation during wound healing

机译:核包膜蛋白Nesprin-2在伤口愈合过程中在细胞增殖和分化中起作用

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摘要

Nesprin-2, a type II transmembrane protein of the nuclear envelope, is a component of the LINC complex that connects the nuclear lamina with the actin cytoskeleton. To elucidate its physiological role we studied wound healing in Nesprin-2 Giant deficient mice and found that a loss of the protein affected wound healing particularly at later stages during fibroblast differentiation and keratinocyte proliferation leading to delayed wound closure. We identified altered expression and localization of transcription factors as one of the underlying mechanisms. Furthermore, the actin cytoskeleton which surrounds the nucleus was altered and keratinocyte migration was slowed down and focal adhesion formation enhanced. We also uncovered a new activity of Nesprin-2. When we probed for an interaction of Nesprin-2 Giant with chromatin we observed in ChIP Seq experiments an association of the protein with heterochromatic and centromeric DNA. Through this activity Nesprin-2 can affect the nuclear landscape and gene regulation. Our findings suggest functions for Nesprin-2 at the nuclear envelope (NE) in gene regulation and in regulation of the actin cytoskeleton which impact on wound healing.
机译:Nesprin-2是核被膜的II型跨膜蛋白,是LINC复合体的一个组成部分,该复合体连接核层和肌动蛋白细胞骨架。为了阐明其生理作用,我们研究了Nesprin-2 Giant缺陷小鼠的伤口愈合,发现蛋白质的损失会影响伤口愈合,尤其是在成纤维细胞分化和角质形成细胞增殖导致伤口闭合延迟的后期。我们确定改变的表达和转录因子的定位是潜在的机制之一。此外,包围核的肌动蛋白细胞骨架被改变,角质形成细胞的迁移被减慢并且粘着斑形成的增强。我们还发现了Nesprin-2的新活性。当我们探究Nesprin-2 Giant与染色质的相互作用时,我们在ChIP Seq实验中观察到了蛋白质与异色和着丝粒DNA的关联。通过这种活动,Nesprin-2可以影响核景观和基因调控。我们的发现表明,Nesprin-2在核膜(NE)的功能中起着基因调节和肌动蛋白细胞骨架调节作用,从而影响伤口愈合。

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