The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy
The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy
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DOI：
10.1016/s0092-8674(02)01226-6
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发表时间：
2002-12-27
期刊：
影响因子：
64.5
通讯作者：
Chien, KR
中科院分区：
文献类型：
--
作者：
Knöll, R;Hoshijima, M;Chien, KR
肌细胞通过触发肌细胞生长和存活的下游信号来响应机械拉伸刺激。肌肉拉伸传感器的分子组成尚不清楚，它们在肌肉疾病中的作用也不清楚。在这里，我们提出了肌肉LIM蛋白（MLP）缺乏心肌的生物物理/生化研究，支持这种Z盘蛋白在机械拉伸传感的选择性作用。MLP与肌联蛋白相互作用蛋白Telethonin（T-cap）相互作用并共定位。此外，与扩张型心肌病（DCM）相关的人MLP突变（W 4 R）导致T-cap相互作用/定位的显著缺陷。我们认为Z盘MLP/T-cap复合物是体内心肌细胞拉伸传感器机制的关键组成部分，并且复合物中的缺陷可导致人类DCM和相关的心力衰竭。
Muscle cells respond to mechanical stretch stimuli by triggering downstream signals for myocyte growth and survival. The molecular components of the muscle stretch sensor are unknown, and their role in muscle disease is unclear. Here, we present biophysical/biochemical studies in muscle LIM protein (MLP) deficient cardiac muscle that support a selective role for this Z disc protein in mechanical stretch sensing. MLP interacts with and colocalizes with telethonin (T-cap), a titin interacting protein. Further, a human MLP mutation (W4R) associated with dilated cardiomyopathy (DCM) results in a marked defect in T-cap interaction/localization. We propose that a Z disc MLP/T-cap complex is a key component of the in vivo cardiomyocyte stretch sensor machinery, and that defects in the complex can lead to human DCM and associated heart failure.