Functional classification of skeletal muscle networks. I. Normal physiology.
Functional classification of skeletal muscle networks. I. Normal physiology.
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骨骼肌网络的功能分类。
DOI：
10.1152/japplphysiol.01514.2011
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Subramaniam,Shankar
中科院分区：
文献类型：
--
作者：
Wang,Yu;Winters,Jack;Subramaniam,Shankar
通过转录组学和其他表型分析对人类骨骼肌部分清单进行广泛的测量，为重建详细的功能模型提供了机会。通过整合数据库中存在的大量数据和现有的肌肉功能知识，结合包括聚类方法在内的稳健分析，我们提出了骨骼肌功能的蛋白质部分列表和网络模型。该模型包括四个在功能空间内共存的关键功能家族网络：即兴奋-激活家族(将运动神经元命令信号传递到细胞空间体积，然后使用钙通量将钙结合到F-肌动蛋白细丝上的肌钙蛋白C位点的前向通路，以及维持传输能力的跨膜泵)；机械传递家族(一个复杂的三维机械装置，将数百万个肌动蛋白纳米运动器与插入部位的外轴向拉力双向耦合)；代谢和生物能量家族(在广泛不同的需求下为骨骼肌功能提供能量并为其他细胞过程提供能量的通路)；以及信号产生家族(代表各种感觉、信号转导和核基础设施，控制肌肉的翻转和结构完整性，并调节肌肉的维护、再生和重塑)。在每个家族中，我们通过分析肌肉和其他组织的大规模转录图谱来识别作为一个单位发挥功能的亚家族。这个全面的网络模型为探索骨骼肌在正常和病理生理学中的作用机制以及定量建模提供了一个框架。
Extensive measurements of the parts list of human skeletal muscle through transcriptomics and other phenotypic assays offer the opportunity to reconstruct detailed functional models. Through integration of vast amounts of data present in databases and extant knowledge of muscle function combined with robust analyses that include a clustering approach, we present both a protein parts list and network models for skeletal muscle function. The model comprises the four key functional family networks that coexist within a functional space; namely, excitation-activation family (forward pathways that transmit a motoneuronal command signal into the spatial volume of the cell and then use Ca2+fluxes to bind Ca2+to troponin C sites on F-actin filaments, plus transmembrane pumps that maintain transmission capacity); mechanical transmission family (a sophisticated three-dimensional mechanical apparatus that bidirectionally couples the millions of actin-myosin nanomotors with external axial tensile forces at insertion sites); metabolic and bioenergetics family (pathways that supply energy for the skeletal muscle function under widely varying demands and provide for other cellular processes); and signaling-production family (which represents various sensing, signal transduction, and nuclear infrastructure that controls the turn over and structural integrity and regulates the maintenance, regeneration, and remodeling of the muscle). Within each family, we identify subfamilies that function as a unit through analysis of large-scale transcription profiles of muscle and other tissues. This comprehensive network model provides a framework for exploring functional mechanisms of the skeletal muscle in normal and pathophysiology, as well as for quantitative modeling.