Novel insights into sarcomere regulatory systems control of cardiac thin filament activation.
Novel insights into sarcomere regulatory systems control of cardiac thin filament activation.
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DOI：
10.1085/jgp.202012777
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发表时间：
2021-07-05
期刊：
影响因子：
--
通讯作者：
Solaro RJ
中科院分区：
文献类型：
--
作者：
Solís C;Solaro RJ
本文综述了肌节激活的三态模型中的细丝调节机制，重点是心脏特有的机制，以及带刺末端和尖端的信号级联。我们的综述集中在肌节调节机制上，讨论了对细丝激活的三态模型从阻断到闭合再到开放状态的心脏特异性修改。我们讨论了钙离子、交叉桥相互作用以及粗丝相关蛋白、心肌肌球蛋白结合蛋白C(cMyBP-C)、心脏调节轻链(CRLC)和肌动蛋白(Titin)对这些细丝转变的调节。越来越多的证据支持这样一种观点，即尽管只有一个钙离子触发肌钙蛋白C调控位点(CTNC)，但细丝的协同激活不能孤立于肌小球的其他功能结构域。我们讨论了这些结构域与细丝调控单元之间的长程和短程相互作用，包括Z-Disc上带刺末端的蛋白质和M-带附近的尖端蛋白质。对这些讨论来说，重要的是对cMyBP-C、cRLC和titin细丝的作用的理解不断加深。对这些控制过程的详细了解对于理解在不同血流动力学负荷下维持生理性心脏状态的机制，更好地定义遗传性和获得性心脏疾病，以及在肌节水平上开发治疗靶点至关重要。
This review focuses on thin filament regulatory mechanisms with emphasis on cardiac-specific mechanisms in the three-state model of sarcomere activation and on signaling cascades at the barbed and pointed ends. Our review focuses on sarcomere regulatory mechanisms with a discussion of cardiac-specific modifications to the three-state model of thin filament activation from a blocked to closed to open state. We discuss modulation of these thin filament transitions by Ca2+, by crossbridge interactions, and by thick filament–associated proteins, cardiac myosin–binding protein C (cMyBP-C), cardiac regulatory light chain (cRLC), and titin. Emerging evidence supports the idea that the cooperative activation of the thin filaments despite a single Ca2+ triggering regulatory site on troponin C (cTnC) cannot be considered in isolation of other functional domains of the sarcomere. We discuss long- and short-range interactions among these domains with the regulatory units of thin filaments, including proteins at the barbed end at the Z-disc and the pointed end near the M-band. Important to these discussions is the ever-increasing understanding of the role of cMyBP-C, cRLC, and titin filaments. Detailed knowledge of these control processes is critical to the understanding of mechanisms sustaining physiological cardiac state with varying hemodynamic load, to better defining genetic and acquired cardiac disorders, and to developing targets for therapies at the level of the sarcomeres.
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DOI：
10.1073/pnas.1809540115
发表时间：
2018-08-28
影响因子：
11.1
作者：
Anderson, Robert L.;Trivedi, Darshan V.;Spudich, James A.
通讯作者：
Spudich, James A.
影响因子：
16.6
作者：
Boczkowska M;Rebowski G;Kremneva E;Lappalainen P;Dominguez R
通讯作者：
Dominguez R
影响因子：
3.7
作者：
Bonzo, Jeremy R.;Norris, Andrea A.;Moncman, Carole L.
通讯作者：
Moncman, Carole L.
DOI：
10.1101/sqb.1973.037.01.037
发表时间：
1973-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
BREMEL, RD;MURRAY, JM;WEBER, A
通讯作者：
WEBER, A
影响因子：
3.5
作者：
Carrier L;Mearini G;Stathopoulou K;Cuello F
通讯作者：
Cuello F