Holaska James M
Department of Medicine, Section of Cardiology, University of Chicago, 5841 S Maryland Ave, MC 6088, Chicago, IL 60637, USA.
Circ Res. 2008 Jul 3;103(1):16-23. doi: 10.1161/CIRCRESAHA.108.172197.
The human genome is contained within the nucleus and is separated from the cytoplasm by the nuclear envelope. Mutations in the nuclear envelope proteins emerin and lamin A cause a number of diseases including premature aging syndromes, muscular dystrophy, and cardiomyopathy. Emerin and lamin A are implicated in regulating muscle- and heart-specific gene expression and nuclear architecture. For example, lamin A regulates the expression and localization of gap junction and intercalated disc components. Additionally, emerin and lamin A are also required to maintain nuclear envelope integrity. Demonstrating the importance of maintaining nuclear integrity in heart disease, atrioventricular node cells lacking lamin A exhibit increased nuclear deformation and apoptosis. This review highlights the present understanding of lamin A and emerin function in regulating nuclear architecture, gene expression, and cell signaling and discusses putative mechanisms for how specific mutations in lamin A and emerin cause cardiac- or muscle-specific disease.
人类基因组包含在细胞核内，并通过核膜与细胞质分隔开来。核膜蛋白emerin和核纤层蛋白A的突变会引发多种疾病，包括早衰综合征、肌肉萎缩症和心肌病。Emerin和核纤层蛋白A参与调节肌肉和心脏特异性基因表达以及核结构。例如，核纤层蛋白A调节缝隙连接和闰盘成分的表达与定位。此外，维持核膜完整性也需要emerin和核纤层蛋白A。房室结细胞缺乏核纤层蛋白A时会出现核变形增加和细胞凋亡，这表明维持核完整性在心脏病中具有重要意义。本综述重点介绍了目前对核纤层蛋白A和emerin在调节核结构、基因表达和细胞信号传导方面功能的理解，并讨论了核纤层蛋白A和emerin的特定突变导致心脏或肌肉特异性疾病的可能机制。
