Lamin A/C and emerin regulate MKL1-SRF activity by modulating actin dynamics

摘要

在几乎普遍表达的核包膜蛋白Lamin A／C和rnEmerin中所发生的突变，会导致高度组织特异rn性的疾病，如Emery-DreiftJSS肌肉萎缩症和扩rn张型心肌病。这项研究表明，Lamjns中发生的rn突变，与引起转录因子MKL1(对心脏发育至关rn重要)的异常核转位和下游信号作用的肌动蛋rn白动态的受损有关。这些结果显示了核包膜蛋rn白对细胞过程的多样化影响，同时也表明：纠rn正受损MKL1-SRF信号作用的疗法也许可帮助rn控制与核纤层病变相关的心脏病。%Laminopathies, caused by mutations in the LMNA gene encoding the nuclear envelope proteins lamins A and C, represent a diverse group of diseases that include Emery-Dreifuss muscular dystrophy (EDMD), dilated cardiomyopathy (DCM), limb-girdle muscular dystrophy, and Hutchison-Gilford progeria syndrome~1. Most LMNA mutations affect skeletal and cardiac muscle by mechanisms that remain incompletely understood. Loss of structural function and altered interaction of mutant lamins with (tissue-specific) transcription factors have been proposed to explain the tissue-specific phenotypes~1.