Single Muscle Fiber Proteomics Reveals Distinct Protein Changes in Slow and Fast Fibers during Muscle Atrophy
Single Muscle Fiber Proteomics Reveals Distinct Protein Changes in Slow and Fast Fibers during Muscle Atrophy
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DOI：
10.1021/acs.jproteome.8b00093
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发表时间：
2018-10-01
影响因子：
4.4
通讯作者：
Krueger, Marcus
中科院分区：
文献类型：
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作者：
Lang, Franziska;Khaghani, Solmaz;Krueger, Marcus
骨骼肌由具有不同代谢特征的不同纤维集合组成。由于具有不同的神经支配和纤维类型组成，每块肌肉履行特定的功能，并对刺激和干扰做出不同的反应。我们用质谱仪分析了小鼠坐骨神经切断后失去神经支配后的蛋白质变化。这种蛋白质组学方法使我们能够量化每个比目鱼肌和EDL(指长伸肌)肌纤维中类似的600种蛋白质。肌球蛋白重链(MyHC)在单个纤维中的表达使特定纤维类型得以聚集；比较来自具有相同MyHC表达的对照肌肉和失神经肌肉的纤维发现，在去神经支配7天后，I、-II或-IIb类型纤维中总共240个蛋白质的调节受到限制。几种线粒体和蛋白酶体蛋白的水平明显改变，表明失神经后代谢过程迅速适应。此外，我们观察到参与钙离子结合和运输的蛋白质，如肌钙蛋白、小白蛋白和ATP2A2的纤维类型特异性调节，表明失神经后肌肉收缩能力显著重塑。这项研究为不同类型的肌肉纤维如何在肌肉萎缩期间重塑其蛋白质组提供了新的见解。
Skeletal muscles are composed of heterogeneous collections of fibers with different metabolic profiles. With varied neuronal innervation and fiber-type compositions, each muscle fulfils specific functions and responds differently to stimuli and perturbations. We assessed individual fibers by mass spectrometry to dissect protein changes after loss of neuronal innervation due to section of the sciatic nerve in mice. This proteomics approach enabled us to quantify similar to 600 proteins per individual soleus and EDL (extensor digitorum longus) muscle fiber. Expression of myosin heavy chain (MyHC) in individual fibers enabled clustering of specific fiber types; comparison of fibers from control and denervated muscles with the same MyHC expression revealed restricted regulation of a total of 240 proteins in type-I, -II, or -IIb fibers 7 days after denervation. The levels of several mitochondrial and proteasomal proteins were significantly altered, indicating rapid adaption of metabolic processes after denervation. Furthermore, we observed fiber-type-specific regulation of proteins involved in calcium ion binding and transport, such as troponins, parvalbumin, and ATP2A2, indicating marked remodeling of muscle contractility after denervation. This study provides novel insight into how different muscle fiber types remodel their proteomes during muscular atrophy.