The small muscle-specific protein Csl modifies cell shape and promotes myocyte fusion in an insulin-like growth factor 1-dependent manner.
The small muscle-specific protein Csl modifies cell shape and promotes myocyte fusion in an insulin-like growth factor 1-dependent manner.
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DOI：
10.1083/jcb.153.5.985
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发表时间：
2001-05-28
期刊：
影响因子：
--
通讯作者：
Harvey RP
中科院分区：
文献类型：
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作者：
Palmer S;Groves N;Schindeler A;Yeoh T;Biben C;Wang CC;Sparrow DB;Barnett L;Jenkins NA;Copeland NG;Koentgen F;Mohun T;Harvey RP
我们在筛选心脏同源结构域因子Nkx2-5的转录靶标时，分离到了编码9-kD蛋白Chisel(CSL)的小鼠基因。CSL转录本存在于心脏的心房和心室，以及胃和肺静脉的所有骨骼肌和平滑肌中。CSL蛋白在胎儿肌肉中分布于细胞质中，但在进一步成熟后，肌细胞骨架的胞内型和M线定位变得明显。CSL的靶向破坏没有明显的肌肉表型。然而，在C2C12成肌细胞中的异位表达诱导了片状脂肪的形成，其中CSL蛋白被拴在膜褶皱上。在单层伤口修复实验中，这些细胞的迁移被延缓。表达CSL的成肌细胞分化和融合正常，尽管在胰岛素样生长因子(IGF)-1存在的情况下，它们表现出显著的融合，导致形成大的畸形形成的“肌囊”。转录因子活化T细胞核因子(NFAT)和心肌细胞增强子结合因子(MEF)2的活性也以IGF-1信号依赖的方式增强。CSL的动态细胞骨架定位及其对细胞形态、行为和转录因子活性的主导作用表明，CSL在肌肉细胞在生长、适应和修复过程中协调其结构和功能状态的调节网络中发挥作用。
We have isolated a murine cDNA encoding a 9-kD protein, Chisel (Csl), in a screen for transcriptional targets of the cardiac homeodomain factor Nkx2-5. Csl transcripts were detected in atria and ventricles of the heart and in all skeletal muscles and smooth muscles of the stomach and pulmonary veins. Csl protein was distributed throughout the cytoplasm in fetal muscles, although costameric and M-line localization to the muscle cytoskeleton became obvious after further maturation. Targeted disruption of Csl showed no overt muscle phenotype. However, ectopic expression in C2C12 myoblasts induced formation of lamellipodia in which Csl protein became tethered to membrane ruffles. Migration of these cells was retarded in a monolayer wound repair assay. Csl-expressing myoblasts differentiated and fused normally, although in the presence of insulin-like growth factor (IGF)-1 they showed dramatically enhanced fusion, leading to formation of large dysmorphogenic “myosacs.” The activities of transcription factors nuclear factor of activated T cells (NFAT) and myocyte enhancer–binding factor (MEF)2, were also enhanced in an IGF-1 signaling–dependent manner. The dynamic cytoskeletal localization of Csl and its dominant effects on cell shape and behavior and transcription factor activity suggest that Csl plays a role in the regulatory network through which muscle cells coordinate their structural and functional states during growth, adaptation, and repair.