The influence of myosin phosphorylation on mechanical and metabolical properties of fast twitch skeletal muscle

肌球蛋白磷酸化对快肌骨骼肌机械和代谢特性的影响

• 批准号: 312012-2008
• 负责人: Vandenboom, Rene
• 金额: $ 1.46万
• 依托单位: Brock University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=481096
• 关键词: influence; myosin; phosphorylation; mechanical; metabolical

The primary structural and enzymatic protein of skeletal muscle is the myosin molecule. The basis of skeletal muscle contraction, and thus movement, is the conversion of chemical energy to mechanical energy by the myosin motor molecule. A key structural element of the myosin molecule is the "regulatory light chain" (R-LC). During muscle activity, the R-LC is chemically modified by the addition of a phosphate ion, an enzymatically regulated process known as "myosin R-LC phosphorylation". Biochemical studies indicate that myosin R-LC phosphorylation may alter myosin motor properties to enhance muscle force, a phenomenon called "force potentiation". The aim of my long term research program is to understand how, why and when myosin R-LC phosphorylation-mediated force potentiation modifies mechanical and metabolic aspects of how fatigued and/or unfatigued skeletal muscle functions. To this end we will perform a variety of experiments examining mechanical and metabolic properties of mouse muscle, a common scientific model for this type of work. The special qualities of this work are that we will perform these studies using genetically engineered mice that lack the gene coding for the enzyme that regulates myosin R-LC phosphorylation and which thus do not exhibit myosin R-LC phosphorylation during activity. Use of these "knockout" mice will allow us to study muscle activity in the absence of myosin R-LC phosphorylation, a situation that does not normally occur, and thus allow us to unequivocally determine the influence of this event on muscle function. We believe that an integrative approach examining the interaction of myosin R-LC phosphorylation with muscle mechanics, intracellular calcium homeostasis and muscle energetics, in both knockout and normal mice, will provide key insights into the physiological role and mechanism of action of myosin R-LC phosphorylation for skeletal muscle function. This type of information is vitally important because there is much current interest in how myosin R-LC phosphorylation modulates performance of healthy and diseased human skeletal muscle, and our work will provide important new directions for future work in this area.

骨骼肌的主要结构和酶蛋白是肌球蛋白分子。骨骼肌收缩和运动的基础是肌球蛋白运动分子将化学能转化为机械能。肌球蛋白分子的关键结构元件是“调节轻链”（R-LC）。 在肌肉活动过程中，R-LC通过加入磷酸根离子进行化学修饰，这是一种酶促调节的过程，称为“肌球蛋白R-LC磷酸化”。 生物化学研究表明，肌球蛋白R-LC磷酸化可以改变肌球蛋白运动特性，以增强肌肉力量，这种现象称为“力增强”。 我的长期研究计划的目的是了解肌球蛋白R-LC磷酸化介导的力增强如何，为什么以及何时改变疲劳和/或非疲劳骨骼肌功能的机械和代谢方面。 为此，我们将进行各种实验，检查小鼠肌肉的机械和代谢特性，这是此类工作的常见科学模型。这项工作的特殊之处在于，我们将使用基因工程小鼠进行这些研究，这些小鼠缺乏编码调节肌球蛋白R-LC磷酸化的酶的基因，因此在活动期间不会表现出肌球蛋白R-LC磷酸化。使用这些“敲除”小鼠将使我们能够研究肌球蛋白R-LC磷酸化的情况下，肌肉活动，通常不会发生的情况下，从而使我们能够明确确定这一事件对肌肉功能的影响。我们相信，一个综合的方法检查肌球蛋白R-LC磷酸化与肌肉力学，细胞内钙稳态和肌肉能量学的相互作用，在基因敲除和正常小鼠，将提供关键的洞察肌球蛋白R-LC磷酸化的生理作用和作用机制的骨骼肌功能。 这种类型的信息是非常重要的，因为有很多目前的兴趣，在如何肌球蛋白R-LC磷酸化调节健康和患病的人骨骼肌的性能，我们的工作将提供重要的新方向，为未来的工作在这一领域。