Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Proteomics Group, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Elife. 2020 Mar 4;9:e51406. doi: 10.7554/eLife.51406.
Proteome and transcriptome analyses aim at comprehending the molecular profiles of the brain, its cell-types and subcellular compartments including myelin. Despite the relevance of the peripheral nervous system for normal sensory and motor capabilities, analogous approaches to peripheral nerves and peripheral myelin have fallen behind evolving technical standards. Here we assess the peripheral myelin proteome by gel-free, label-free mass-spectrometry for deep quantitative coverage. Integration with RNA-Sequencing-based developmental mRNA-abundance profiles and neuropathy disease genes illustrates the utility of this resource. Notably, the periaxin-deficient mouse model of the neuropathy Charcot-Marie-Tooth 4F displays a highly pathological myelin proteome profile, exemplified by the discovery of reduced levels of the monocarboxylate transporter MCT1/SLC16A1 as a novel facet of the neuropathology. This work provides the most comprehensive proteome resource thus far to approach development, function and pathology of peripheral myelin, and a straightforward, accurate and sensitive workflow to address myelin diversity in health and disease.
蛋白质组和转录组分析旨在理解大脑的分子特征、细胞类型和亚细胞区室，包括髓鞘。尽管周围神经系统对正常的感觉和运动功能至关重要，但类似的针对周围神经和周围髓鞘的方法已经落后于不断发展的技术标准。在这里，我们通过无胶、无标记的质谱法评估了髓鞘的蛋白质组，以实现深度定量覆盖。与基于 RNA 测序的发育 mRNA 丰度图谱和神经病基因的整合说明了这一资源的实用性。值得注意的是，神经病 Charcot-Marie-Tooth 4F 的脱髓鞘蛋白缺失小鼠模型显示出高度病理性的髓鞘蛋白质组特征，发现单羧酸转运蛋白 MCT1/SLC16A1 的水平降低就是神经病理学的一个新方面。这项工作提供了迄今为止最全面的蛋白质组资源，用于研究周围髓鞘的发育、功能和病理学，以及一种简单、准确和敏感的工作流程，用于解决健康和疾病中髓鞘的多样性问题。
