Wheeler Matthew A, Ellis Juliet A
Randall Division of Cell and Molecular Biophysics, King's College, New Hunt's House, London, UK.
Biochem Soc Trans. 2008 Dec;36(Pt 6):1354-8. doi: 10.1042/BST0361354.
Mutations in genes encoding the nuclear envelope proteins emerin and lamin A/C lead to a range of tissue-specific degenerative diseases. These include dilated cardiomyopathy, limb-girdle muscular dystrophy and X-linked and autosomal dominant EDMD (Emery-Dreifuss muscular dystrophy). The molecular mechanisms underlying these disorders are poorly understood; however, recent work using animal models has identified a number of signalling pathways that are altered in response to the deletion of either emerin or lamin A/C or expression of Lmna mutants found in patients with laminopathies. A distinguishing feature of patients with EDMD is the association of a dilated cardiomyopathy with conduction defects. In the present article, we describe several of the pathways altered in response to an EDMD phenotype, which are known to be key mediators of hypertrophic growth, and focus on a possible role of an emerin-beta-catenin interaction in the pathogenesis of this disease.
编码核膜蛋白埃默菌素和核纤层蛋白A/C的基因突变会导致一系列组织特异性退行性疾病。这些疾病包括扩张型心肌病、肢带型肌营养不良以及X连锁和常染色体显性Emery-Dreifuss肌营养不良（EDMD）。这些病症背后的分子机制目前还知之甚少；然而，最近利用动物模型开展的研究已经确定了一些信号通路，这些信号通路会因埃默菌素或核纤层蛋白A/C的缺失或在核纤层蛋白病患者中发现的Lmna突变体的表达而发生改变。EDMD患者的一个显著特征是扩张型心肌病与传导缺陷相关。在本文中，我们描述了因EDMD表型而发生改变的几条通路，这些通路已知是肥厚性生长的关键介质，并重点探讨了埃默菌素-β-连环蛋白相互作用在该疾病发病机制中的可能作用。
