Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Wiley Interdiscip Rev Syst Biol Med. 2013 Jan-Feb;5(1):55-71. doi: 10.1002/wsbm.1197. Epub 2012 Nov 27.
Skeletal muscle function depends on the efficient coordination among subcellular systems. These systems are composed of proteins encoded by a subset of genes, all of which are tightly regulated. In the cases where regulation is altered because of disease or injury, dysfunction occurs. To enable objective analysis of muscle gene expression profiles, we have defined nine biological networks whose coordination is critical to muscle function. We begin by describing the expression of proteins necessary for optimal neuromuscular junction function that results in the muscle cell action potential. That action potential is transmitted to proteins involved in excitation-contraction coupling enabling Ca(2+) release. Ca(2+) then activates contractile proteins supporting actin and myosin cross-bridge cycling. Force generated by cross-bridges is transmitted via cytoskeletal proteins through the sarcolemma and out to critical proteins that support the muscle extracellular matrix. Muscle contraction is fueled through many proteins that regulate energy metabolism. Inflammation is a common response to injury that can result in alteration of many pathways within muscle. Muscle also has multiple pathways that regulate size through atrophy or hypertrophy. Finally, the isoforms associated with fast muscle fibers and their corresponding isoforms in slow muscle fibers are delineated. These nine networks represent important biological systems that affect skeletal muscle function. Combining high-throughput systems analysis with advanced networking software will allow researchers to use these networks to objectively study skeletal muscle systems.
骨骼肌的功能取决于细胞内系统之间的有效协调。这些系统由一组基因中的一部分编码的蛋白质组成，所有这些蛋白质都受到严格的调控。如果由于疾病或损伤导致调节发生改变，就会出现功能障碍。为了能够对肌肉基因表达谱进行客观分析，我们定义了九个生物学网络，它们的协调对于肌肉功能至关重要。我们首先描述了对最佳神经肌肉接头功能所必需的蛋白质的表达，这会导致肌肉细胞动作电位的产生。该动作电位被传递到参与兴奋-收缩偶联的蛋白质，从而实现 Ca(2+)的释放。然后，Ca(2+)激活支持肌动蛋白和肌球蛋白横桥循环的收缩蛋白。横桥产生的力通过细胞骨架蛋白穿过肌膜传递到支持肌肉细胞外基质的关键蛋白上。肌肉收缩通过许多调节能量代谢的蛋白质来提供动力。炎症是对损伤的常见反应，可能导致肌肉内许多途径的改变。肌肉还具有多种调节大小的途径，包括萎缩或肥大。最后，阐明了与快肌纤维相关的同工型及其在慢肌纤维中的对应同工型。这九个网络代表了影响骨骼肌功能的重要生物学系统。将高通量系统分析与先进的网络软件相结合，将使研究人员能够使用这些网络来客观地研究骨骼肌系统。
