From the ‡Laboratoire Proteomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM) - INSERM U1192, Université Lille 1, Bât SN3, 1 étage, Cité Scientifique, F-59655 Villeneuve d'Ascq Cedex, France.
§Département de Biochimie Lab. Z8-2001, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Canada.
Mol Cell Proteomics. 2018 Feb;17(2):357-372. doi: 10.1074/mcp.M116.065755. Epub 2017 Nov 9.
Tissue spatially-resolved proteomics was performed on 3 brain regions, leading to the characterization of 123 reference proteins. Moreover, 8 alternative proteins from alternative open reading frames (AltORF) were identified. Some proteins display specific post-translational modification profiles or truncation linked to the brain regions and their functions. Systems biology analysis performed on the proteome identified in each region allowed to associate sub-networks with the functional physiology of each brain region. Back correlation of the proteins identified by spatially-resolved proteomics at a given tissue localization with the MALDI MS imaging data, was then performed. As an example, mapping of the distribution of the matrix metallopeptidase 3-cleaved C-terminal fragment of α-synuclein (aa 95-140) identified its specific distribution along the hippocampal dentate gyrus. Taken together, we established the molecular physiome of 3 rat brain regions through reference and hidden proteome characterization.
对 3 个脑区进行了组织的空间分辨蛋白质组学研究，鉴定出了 123 种参考蛋白。此外，还鉴定出了 8 种来自选择性开放阅读框（AltORF）的替代蛋白。一些蛋白表现出特定的翻译后修饰谱或与脑区及其功能相关的截断。在每个区域中鉴定的蛋白质组进行系统生物学分析，可将子网络与每个脑区的功能生理学联系起来。然后对在特定组织定位处通过空间分辨蛋白质组学鉴定的蛋白与 MALDI MS 成像数据进行反向相关性分析。例如，对α-突触核蛋白（aa 95-140）的基质金属蛋白酶 3 切割的 C 末端片段的分布进行映射，确定了其沿着海马齿状回的特定分布。总之，我们通过参考和隐藏蛋白质组的鉴定，建立了 3 个大鼠脑区的分子生理学模型。
