Damato Marina, Cardon Tristan, Wisztorski Maxence, Fournier Isabelle, Pieragostino Damiana, Cicalini Ilaria, Salzet Michel, Vergara Daniele, Maffia Michele
Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy.
Laboratory of Clinical Proteomics, "Giovanni Paolo II" Hospital, 73100 ASL-Lecce, Italy.
Int J Mol Sci. 2021 May 15;22(10):5245. doi: 10.3390/ijms22105245.
Protein kinase C (PKC) activation induces cellular reprogramming and differentiation in various cell models. Although many effectors of PKC physiological actions have been elucidated, the molecular mechanisms regulating oligodendrocyte differentiation after PKC activation are still unclear. Here, we applied a liquid chromatography-mass spectrometry (LC-MS/MS) approach to provide a comprehensive analysis of the proteome expression changes in the MO3.13 oligodendroglial cell line after PKC activation. Our findings suggest that multiple networks that communicate and coordinate with each other may finally determine the fate of MO3.13 cells, thus identifying a modular and functional biological structure. In this work, we provide a detailed description of these networks and their participating components and interactions. Such assembly allows perturbing each module, thus describing its physiological significance in the differentiation program. We applied this approach by targeting the Rho-associated protein kinase (ROCK) in PKC-activated cells. Overall, our findings provide a resource for elucidating the PKC-mediated network modules that contribute to a more robust knowledge of the molecular dynamics leading to this cell fate transition.
蛋白激酶C（PKC）的激活在各种细胞模型中诱导细胞重编程和分化。尽管PKC生理作用的许多效应器已被阐明，但PKC激活后调节少突胶质细胞分化的分子机制仍不清楚。在这里，我们应用液相色谱-质谱联用（LC-MS/MS）方法，对PKC激活后MO3.13少突胶质细胞系中的蛋白质组表达变化进行全面分析。我们的研究结果表明，相互沟通和协调的多个网络最终可能决定MO3.13细胞的命运，从而确定一个模块化的功能性生物结构。在这项工作中，我们详细描述了这些网络及其参与的组件和相互作用。这种组装允许扰动每个模块，从而描述其在分化程序中的生理意义。我们通过靶向PKC激活细胞中的Rho相关蛋白激酶（ROCK）应用了这种方法。总体而言，我们的研究结果为阐明PKC介导的网络模块提供了资源，有助于更深入地了解导致这种细胞命运转变的分子动力学。
