核骨架与细胞骨架的连接体复合体在核纤层蛋白病中的研究进展

Research Progress of Linker of Nucleoskeleton and Cytoskeleton Complex in Laminopathies

核骨架与细胞骨架的连接体(LINC)广泛存在于真核生物中,是建立核膜内外联系的重要复合体。LINC复合体具有维持细胞核形态与定位、传导核骨架与细胞骨架之间机械力、调节基因表达等作用。人肌肉细胞中的LINC复合体若发生缺陷,不仅会造成细胞核的固定、迁移等细胞层面的活动失常,还会由于肌肉细胞内部结构松散使机械力无法正常传导,从而导致Emery-Dreifuss肌营养不良综合征、扩张型心肌病和遗传性运动感觉神经病变等疾病。然而,目前对于这些疾病仍缺乏有效的治疗方法,因此亟须深入研究LINC复合体的功能与致病机制。

The linker of nucleoskeleton and cytoskeleton(LINC)widely exists in many eukaryotes and is an important protein complex associating the nucleus and the cytoplasm.The LINC complex plays roles in nucleus shape and positioning,mechanotransduction,gene regulation,etc.If the LINC complex is defective in human muscle cells,the nucleus would fail to tether and migrate within the cell.More importantly,it will interrupt the transduction of mechanical forces due to the loose structure within muscular cells,further leading to Emery-Dreifuss muscular dystrophy,dilated cardiomyopathy,hereditary motor neuropathy and other diseases.However,effective strategies are absent for the treatment of these diseases.Therefore,further studies on the functions and pathogenic mechanisms of the LINC complex are in urgent need.