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首页> 外文期刊>American Journal of Physiology >Mechanical stress-strain sensors embedded in cardiac cytoskeleton: Z disk, titin, and associated structures.
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Mechanical stress-strain sensors embedded in cardiac cytoskeleton: Z disk, titin, and associated structures.

机译：嵌入心脏细胞骨架的机械应力应变传感器：Z盘，钛蛋白和相关结构。

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Cardiac muscle is equipped with intricate intrinsic mechanisms to regulate adaptive remodeling. Recent and extensive experimental findings powered by novel strategies for screening protein-protein interactions, improved imaging technologies, and versatile transgenic mouse methodologies reveal that Z disks and titin filaments possess unexpectedly complicated sensory and modulatory mechanisms for signal reception and transduction. These mechanisms employ molecules such as muscle-enriched LIM domain proteins, PDZ-LIM domain proteins, myozenin gene family members, titin-associated ankyrin repeat family proteins, and muscle-specific ring finger proteins, which have been identified as potential molecular sensor components. Moreover, classic transmembrane signaling processes, including mitogen-activated kinase, protein kinase C, and calcium signaling, also involve novel interactions with the Z disk/titin network. This compartmentalization of signaling complexes permits alteration of receptor-dependent transcriptional regulation by direct sensing of intrinsic stress. Newly identified mechanical stress sensors are not limited to Z-disk region and to I-band and M-band regions of titin but are also embedded in muscle-specific membrane systems such as the costamere, intercalated disks, and caveolae-like microdomains. This review summarizes current knowledge of this rapidly developing area with focus on how the heart adjusts physiological remodeling process to meet with mechanical demands and how this process fails in cardiac pathologies.
机译：心脏肌肉具有复杂的内在机制来调节适应性重塑。最近和广泛的实验发现，由筛选蛋白质-蛋白质相互作用的新策略，改进的成像技术以及通用的转基因小鼠方法提供动力，表明Z盘和钛蛋白丝具有意想不到的复杂信号接收和转导感觉和调节机制。这些机制利用分子，例如富含肌肉的LIM结构域蛋白，PDZ-LIM结构域蛋白，肌成蛋白基因家族成员，与肌动蛋白相关的锚蛋白重复家族蛋白和肌肉特异性无名指蛋白，这些分子已被鉴定为潜在的分子传感器组件。此外，经典的跨膜信号传导过程，包括促分裂原活化激酶，蛋白激酶C和钙信号传导，也涉及与Z盘/ titin网络的新型相互作用。信号复合物的这种分隔允许通过直接感测内在压力来改变受体依赖性转录调节。新近确定的机械应力传感器不仅限于肌钙蛋白的Z盘区域和I带和M带区域，而且还嵌入到肌肉特定的膜系统中，例如肋肌，插层盘和小窝状微区。这篇综述总结了这一快速发展领域的当前知识，重点是心脏如何调整生理重塑过程以满足机械需求，以及该过程在心脏病理中如何失败。

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