骨骼肌
多核
心肌细胞
细胞生物学
生物
微管组织中心
基因亚型
微管
细胞骨架
肌病
核蛋白
肌肉萎缩
核定位序列
肌肉疾病
肌球蛋白
肌肉组织
ITGA7型
功能(生物学)
肌营养不良
蛋白质生物合成
MyoD公司
肌萎缩
解剖
中心体
细胞
遗传学
核心
内科学
基因
转录因子
医学
细胞周期
作者
Jianming Liu,Zeping Huang,Mao Nie,Gang Wang,William J. Silva,Qianying Yang,Paula Paccielli Freire,Xiaoyun Hu,Huaqun Chen,Zhong‐Liang Deng,William T. Pu,Dazhi Wang
标识
DOI:10.1073/pnas.1922911117
摘要
The appropriate arrangement of myonuclei within skeletal muscle myofibers is of critical importance for normal muscle function, and improper myonuclear localization has been linked to a variety of skeletal muscle diseases, such as centronuclear myopathy and muscular dystrophies. However, the molecules that govern myonuclear positioning remain elusive. Here, we report that skeletal muscle-specific CIP (sk-CIP) is a regulator of nuclear positioning. Genetic deletion of sk-CIP in mice results in misalignment of myonuclei along the myofibers and at specialized structures such as neuromuscular junctions (NMJs) and myotendinous junctions (MTJs) in vivo, impairing myonuclear positioning after muscle regeneration, leading to severe muscle dystrophy in mdx mice, a mouse model of Duchenne muscular dystrophy. sk-CIP is localized to the centrosome in myoblasts and relocates to the outer nuclear envelope in myotubes upon differentiation. Mechanistically, we found that sk-CIP interacts with the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex and the centriole Microtubule Organizing Center (MTOC) proteins to coordinately modulate myonuclear positioning and alignment. These findings indicate that sk-CIP may function as a muscle-specific anchoring protein to regulate nuclear position in multinucleated muscle cells.
科研通智能强力驱动
Strongly Powered by AbleSci AI