Heart-specific localization of emerin: new insights into Emery-Dreifuss muscular dystrophy
Heart-specific localization of emerin: new insights into Emery-Dreifuss muscular dystrophy
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DOI：
10.1093/hmg/6.13.2257
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发表时间：
1997-12-01
影响因子：
3.5
通讯作者：
Toniolo, D
中科院分区：
文献类型：
--
作者：
Cartegni, L;diBarletta, MR;Toniolo, D
emry - dreifuss肌营养不良症（EDMD）是一种x连锁遗传性疾病，其特征是早期肘部、跟腱和颈后肌肉挛缩，缓慢进行性肌肉萎缩和无力，心肌病表现为心律失常和心房麻痹。EDMD基因编码一种新的无所不在的蛋白，emerin，它装饰许多细胞类型的核边缘，氨基酸序列同源性和细胞定位表明emerin是核层相关蛋白家族的成员，这些发现不能解释emerin的作用，也不能解释与该疾病相关的骨骼肌和心脏特异性临床表现。现在，我们报道了emerin通过其疏水c端结构域定位于核膜内，但在心脏和培养的心肌细胞中，它也与嵌入盘有关。我们提出了emerin在细胞骨架的膜锚定中的一般作用。在核膜中，emerin在核膜与层的结合中起着无处不在且不可或缺的作用。在心脏中，它的特异性定位于桥粒和筋膜粘附物，可以解释患者所描述的特征性传导缺陷。
Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked inherited disease characterized by early contracture of the elbows, Achilles tendons and post-cervical muscles, slow progressive muscle wasting and weakness and cardiomyopathy presenting with arrhythmia and atrial paralysis: heart block can eventually lead to sudden death, The EDMD gene encodes a novel ubiquitous protein, emerin, which decorates the nuclear rim of many cell types, Amino acid sequence homology and cellular localization suggested that emerin is a member of the nuclear lamina-associated protein family, These findings did not explain the role of emerin nor account for the skeletal muscle-and heart-specific clinical manifestations associated with the disorder, Now we report that emerin localizes to the inner nuclear membrane, via its hydrophobic C-terminal domain, but that in heart and cultured cardiomyocytes it is also associated with the intercalated discs, We propose a general role for emerin in membrane anchorage to the cytoskeleton, In the nuclear envelope emerin plays a ubiquitous and dispensable role in association of the nuclear membrane with the lamina, In heart its specific localization to desmosomes and fasciae adherentes could account for the characteristic conduction defects described in patients.