Prelamin A-mediated recruitment of SUN1 to the nuclear envelope directs nuclear positioning in human muscle.
Prelamin A-mediated recruitment of SUN1 to the nuclear envelope directs nuclear positioning in human muscle.
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DOI：
10.1038/cdd.2010.183
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发表时间：
2011-08
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
--
作者：
层粘连蛋白A是一种核膜成分，在分化的细胞中表达。LMNA基因的突变会导致几种疾病，包括肌营养不良症和心肌病。层蛋白A的核膜伙伴包括SUN1和SUN2，它们介导了对细胞核锚定至关重要的核-细胞骨架相互作用。在这项研究中，我们发现分化的人成肌细胞积累了法尼化的Prelamin A，这引起了SUN1的上调和核膜上的募集，并有利于SUN2在核极的浓缩。事实上，前层蛋白A法尼化的损伤改变了SUN1的募集和SUN2的定位。此外，在缺乏法尼化前层蛋白A的情况下，肌管中的核定位受到严重影响。重要的是，在Emery-Dreifuss肌营养不良症成肌细胞中观察到前层蛋白A和SUN1水平降低，伴随着肌核定位的改变。这些结果表明，SUN1和法尼化的前层蛋白A之间的相互作用有助于人类肌纤维的核定位，并可能与发病机制有关。
Lamin A is a nuclear lamina constituent expressed in differentiated cells. Mutations in the LMNA gene cause several diseases, including muscular dystrophy and cardiomyopathy. Among nuclear envelope partners of lamin A are SUN1 and SUN2, which mediate nucleo-cytoskeleton interactions critical to the anchorage of nuclei. In this study, we show that differentiating human myoblasts accumulate farnesylated prelamin A, which elicits upregulation and recruitment of SUN1 to the nuclear envelope and favors SUN2 enrichment at the nuclear poles. Indeed, impairment of prelamin A farnesylation alters SUN1 recruitment and SUN2 localization. Moreover, nuclear positioning in myotubes is severely affected in the absence of farnesylated prelamin A. Importantly, reduced prelamin A and SUN1 levels are observed in Emery-Dreifuss muscular dystrophy myoblasts, concomitant with altered myonuclear positioning. These results demonstrate that the interplay between SUN1 and farnesylated prelamin A contributes to nuclear positioning in human myofibers and may be implicated in pathogenetic mechanisms.
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影响因子：
7.8
作者：
Milner, DJ;Weitzer, G;Tran, D;Bradley, A;Capetanaki, Y
通讯作者：
Capetanaki, Y
DOI：
10.1074/jbc.m109.071910
发表时间：
2010-01-29
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Haque F;Mazzeo D;Patel JT;Smallwood DT;Ellis JA;Shanahan CM;Shackleton S
通讯作者：
Shackleton S
影响因子：
3.4
作者：
Hale, Christopher M.;Shrestha, Arun L.;Wirtz, Denis
通讯作者：
Wirtz, Denis
DOI：
10.1016/j.bbamcr.2008.09.001
发表时间：
2008-12-01
影响因子：
5.1
作者：
Lu, Wenshu;Gotzmann, Josef;Karakesisoglou, Iakowos
通讯作者：
Karakesisoglou, Iakowos
影响因子：
2.7
作者：
Capanni, Cristina;Del Coco, Rosalba;Lattanzi, Giovanna
通讯作者：
Lattanzi, Giovanna