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研究发现C18ORF25作为AMPK底物调节骨骼肌功能
2022-07-27 14:43

澳大利亚墨尔本大学Benjamin L. Parker、丹麦哥本哈根大学Erik A. Richter和Bente Kiens共同合作,近期取得重要工作进展,他们利用三种不同运动方式下的磷酸蛋白质组学确定了典型的信号传导,并发现C18ORF25作为AMPK底物来调节骨骼肌的功能。相关论文2022年7月25日在线发表于《细胞—代谢》杂志上。

为了在不同运动方式期间和之后识别不同和共同的信号网络,研究人员对耐力、短跑冲刺和阻力运动的交叉干预的人类骨骼肌进行了磷酸蛋白质组学分析。这确定了在至少一种类型的运动方式期间或之后调节的5,486个磷酸位点,而只有420个核心磷酸位点在所有运动中普遍存在。这些核心磷酸位点之一是未表征的蛋白质C18ORF25上的S67,研究人员将其验证为AMPK底物。

缺乏C18ORF25的小鼠骨骼肌纤维大小、运动能力和肌肉收缩功能降低,这与收缩蛋白和Ca2+处理蛋白的磷酸化降低有关。C18ORF25 S66/67D磷酸模拟物的表达逆转了肌肉力量产生的下降。这项工作定义了跨不同模式下的差异和经典的运动磷酸蛋白质组,并将C18ORF25确定为运动信号和肌肉功能的调节剂。

据介绍,运动可诱导信号网络改善肌肉功能并带来健康益处。

附:英文原文

Title: Phosphoproteomics of three exercise modalities identifies canonical signaling and C18ORF25 as an AMPK substrate regulating skeletal muscle function

Author: Ronnie Blazev, Christian S. Carl, Yaan-Kit Ng, Jeffrey Molendijk, Christian T. Voldstedlund, Yuanyuan Zhao, Di Xiao, Andrew J. Kueh, Paula M. Miotto, Vanessa R. Haynes, Justin P. Hardee, Jin D. Chung, James W. McNamara, Hongwei Qian, Paul Gregorevic, Jonathan S. Oakhill, Marco J. Herold, Thomas E. Jensen, Leszek Lisowski, Gordon S. Lynch, Garron T. Dodd, Matthew J. Watt, Pengyi Yang, Bente Kiens, Erik A. Richter, Benjamin L. Parker

Issue&Volume: 2022-07-25

Abstract: Exercise induces signaling networks to improve muscle function and confer health benefits. To identify divergent and common signaling networks during and after different exercise modalities, we performed a phosphoproteomic analysis of human skeletal muscle from a cross-over intervention of endurance, sprint, and resistance exercise. This identified 5,486 phosphosites regulated during or after at least one type of exercise modality and only 420 core phosphosites common to all exercise. One of these core phosphosites was S67 on the uncharacterized protein C18ORF25, which we validated as an AMPK substrate. Mice lacking C18ORF25 have reduced skeletal muscle fiber size, exercise capacity, and muscle contractile function, and this was associated with reduced phosphorylation of contractile and Ca2+ handling proteins. Expression of C18ORF25 S66/67D phospho-mimetic reversed the decreased muscle force production. This work defines the divergent and canonical exercise phosphoproteome across different modalities and identifies C18ORF25 as a regulator of exercise signaling and muscle function.

DOI: 10.1016/j.cmet.2022.07.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00302-3

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:31.373
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx


本期文章:《细胞—代谢》:Online/在线发表

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