Is titin a 'winding filament'? A new twist on muscle contraction
Is titin a 'winding filament'? A new twist on muscle contraction
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DOI：
10.1098/rspb.2011.1304
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发表时间：
2012-03-07
影响因子：
4.7
通讯作者：
Lindstedt, Stan L.
中科院分区：
文献类型：
--
作者：
Nishikawa, Kiisa C.;Monroy, Jenna A.;Lindstedt, Stan L.
最近的研究表明弹性蛋白titin在活动肌肉中起作用，但其发挥作用的机制仍有待阐明。在活跃的肌肉中，Ca2+结合已被证明增加了titin刚度，但观察到的增加太小，无法解释平行弹性元件在肌肉激活时增加的刚度。我们提出了titin在活动肌肉中的作用的“缠绕丝”机制。首先，我们假设titin的N2A区域与细丝的Ca2+依赖性结合通过防止被动拉伸期间发生的近端免疫球蛋白结构域的低力拉直来增加titin的刚度。这一机制解释了骨骼肌原纤维和心肌细胞对力的长度依赖性的差异。其次，我们假设交叉桥不仅可以作为将细丝拉向m线的马达，还可以作为在细丝上放置titin的转子，在力发展和主动拉伸期间在PEVK中存储弹性势能。在力发展过程中储存的能量可以在主动缩短过程中恢复。缠绕丝假说解释了拉伸过程中的力增强和缩短过程中的力抑制，并提供了可测试的预测，为肌肉收缩机制的研究提供了新的方向。
Recent studies have demonstrated a role for the elastic protein titin in active muscle, but the mechanisms by which titin plays this role remain to be elucidated. In active muscle, Ca2+-binding has been shown to increase titin stiffness, but the observed increase is too small to explain the increased stiffness of parallel elastic elements upon muscle activation. We propose a 'winding filament' mechanism for titin's role in active muscle. First, we hypothesize that Ca2+-dependent binding of titin's N2A region to thin filaments increases titin stiffness by preventing low-force straightening of proximal immunoglobulin domains that occurs during passive stretch. This mechanism explains the difference in length dependence of force between skeletal myofibrils and cardiac myocytes. Second, we hypothesize that cross-bridges serve not only as motors that pull thin filaments towards the M-line, but also as rotors that wind titin on the thin filaments, storing elastic potential energy in PEVK during force development and active stretch. Energy stored during force development can be recovered during active shortening. The winding filament hypothesis accounts for force enhancement during stretch and force depression during shortening, and provides testable predictions that will encourage new directions for research on mechanisms of muscle contraction.