Phosphoproteomics of three exercise modalities identifies canonical signaling and C18ORF25 as anAMPK substrate regulating skeletal muscle function
Phosphoproteomics of three exercise modalities identifies canonical signaling and C18ORF25 as anAMPK substrate regulating skeletal muscle function
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DOI：
10.1016/j.cmet.2022.07.003
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发表时间：
2022-10-04
期刊：
影响因子：
29
通讯作者：
Parker, Benjamin L.
中科院分区：
文献类型：
--
作者：
Blazev, Ronnie;Carl, Christian S.;Parker, Benjamin L.
运动会诱导信号网络改善肌肉功能并带来健康益处。为了确定不同运动方式期间和之后不同和共同的信号网络，我们对耐力、冲刺和抗阻运动的交叉干预中的人类骨骼肌进行了磷酸蛋白质组学分析。这确定了至少一种运动方式期间或之后受到调节的 5,486 个磷酸位点，以及所有运动共有的 420 个核心磷酸位点。这些核心磷酸位点之一是未表征的蛋白质 C18ORF25 上的 S67，我们将其验证为 AMPK 底物。缺乏 C18ORF25 的小鼠骨骼肌纤维尺寸、运动能力和肌肉收缩功能均降低，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减少。这项工作定义了不同模式下不同且规范的运动磷酸化蛋白质组，并将 C18ORF25 确定为运动信号和肌肉功能的调节因子。
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.