The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles.
The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles.
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DOI：
10.1007/s12551-021-00836-3
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发表时间：
2021-10
影响因子：
--
通讯作者：
Lange S
中科院分区：
文献类型：
--
作者：
van der Pijl RJ;Domenighetti AA;Sheikh F;Ehler E;Ottenheijm CAC;Lange S
肌肉特异性信号已被证明起源于肌丝及其相关的细胞结构，包括肌节、腔骨或心脏间盘。在心肌和/或骨骼肌生理学中发挥重要生物力学作用的两个信号枢纽是巨型蛋白titin中的N2B和N2A区域。与Titin中这些区域相关的主要蛋白质是伴侣蛋白Hsp90和αB晶体蛋白，它们是四个半LIM(FHL)和肌肉骨架蛋白重复蛋白(ANKRD)家族的成员，以及细丝相关蛋白，如myopalladin。这篇综述重点介绍了titin N2B和N2A区域在健康和疾病中的生物学作用和性质。特别强调Ankrd和FHL蛋白作为机械传感器的功能，调节肌肉特定的信号和肌肉生长。肌节的这一区域也成为通过改变肌蛋白的磷酸化和剪接，以及将肌蛋白连接到细丝系统的拴系机制来调节被动肌肉力学的热点。
Muscle specific signaling has been shown to originate from myofilaments and their associated cellular structures, including the sarcomeres, costameres or the cardiac intercalated disc. Two signaling hubs that play important biomechanical roles for cardiac and/or skeletal muscle physiology are the N2B and N2A regions in the giant protein titin. Prominent proteins associated with these regions in titin are chaperones Hsp90 and αB-crystallin, members of the four-and-a-half LIM (FHL) and muscle ankyrin repeat protein (Ankrd) families, as well as thin filament-associated proteins, such as myopalladin. This review highlights biological roles and properties of the titin N2B and N2A regions in health and disease. Special emphasis is placed on functions of Ankrd and FHL proteins as mechanosensors that modulate muscle-specific signaling and muscle growth. This region of the sarcomere also emerged as a hotspot for the modulation of passive muscle mechanics through altered titin phosphorylation and splicing, as well as tethering mechanisms that link titin to the thin filament system.
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