Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, Georgia, USA.
Curr Top Dev Biol. 2011;96:273-302. doi: 10.1016/B978-0-12-385940-2.00010-3.
Proper skeletal muscle function is dependent on spatial and temporal control of gene expression in multinucleated myofibers. In addition, satellite cells, which are tissue-specific stem cells that contribute critically to repair and maintenance of skeletal muscle, are also required for normal muscle physiology. Gene expression in both myofibers and satellite cells is dependent upon nuclear proteins that require facilitated nuclear transport. A unique challenge for myofibers is controlling the transcriptional activity of hundreds of nuclei in a common cytoplasm yet achieving nuclear selectivity in transcription at specific locations such as neuromuscular synapses and myotendinous junctions. Nucleocytoplasmic transport of macromolecular cargoes is regulated by a complex interplay among various components of the nuclear transport machinery, namely nuclear pore complexes, nuclear envelope proteins, and various soluble transport receptors. The focus of this review is to highlight what is known about the nuclear transport machinery and its regulation in skeletal muscle and to consider the unique challenges that multinucleated muscle cells as well as satellite cells encounter in regulating nucleocytoplasmic transport during cell differentiation and tissue adaptation. Understanding how regulated nucleocytoplasmic transport controls gene expression in skeletal muscle may lead to further insights into the mechanisms contributing to muscle growth and maintenance throughout the lifespan of an individual.
适当的骨骼肌功能依赖于多核肌纤维中基因表达的时空控制。此外,卫星细胞是组织特异性干细胞,对骨骼肌的修复和维持至关重要,也是正常肌肉生理学所必需的。肌纤维和卫星细胞中的基因表达都依赖于需要促进核转运的核蛋白。对于肌纤维来说,一个独特的挑战是在共同的细胞质中控制数百个核的转录活性,但要在特定位置(如神经肌肉突触和肌-腱连接处)实现核选择性转录。大分子货物的核质转运受核转运机制的各种成分之间复杂的相互作用调节,即核孔复合物、核膜蛋白和各种可溶性转运受体。本综述的重点是强调已知的核转运机制及其在骨骼肌中的调节作用,并考虑多核肌肉细胞以及卫星细胞在细胞分化和组织适应过程中调节核质转运时所面临的独特挑战。了解受调控的核质转运如何控制骨骼肌中的基因表达,可能有助于进一步了解在个体的整个生命周期中促进肌肉生长和维持的机制。