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Cell type-selective secretome profiling in vivo.

细胞类型-体内选择性分泌组谱。

  • 影响因子:9.33
  • DOI:10.1038/s41589-020-00698-y
  • 作者列表:"Wei W","Riley NM","Yang AC","Kim JT","Terrell SM","Li VL","Garcia-Contreras M","Bertozzi CR","Long JZ
  • 发表时间:2021-03-01
Abstract

:Secreted polypeptides are a fundamental axis of intercellular and endocrine communication. However, a global understanding of the composition and dynamics of cellular secretomes in intact mammalian organisms has been lacking. Here, we introduce a proximity biotinylation strategy that enables labeling, detection and enrichment of secreted polypeptides in a cell type-selective manner in mice. We generate a proteomic atlas of hepatocyte, myocyte, pericyte and myeloid cell secretomes by direct purification of biotinylated secreted proteins from blood plasma. Our secretome dataset validates known cell type-protein pairs, reveals secreted polypeptides that distinguish between cell types and identifies new cellular sources for classical plasma proteins. Lastly, we uncover a dynamic and previously undescribed nutrient-dependent reprogramming of the hepatocyte secretome characterized by the increased unconventional secretion of the cytosolic enzyme betaine-homocysteine S-methyltransferase (BHMT). This secretome profiling strategy enables dynamic and cell type-specific dissection of the plasma proteome and the secreted polypeptides that mediate intercellular signaling.

摘要

: 分泌多肽是细胞间和内分泌通讯的基本轴。然而,对完整哺乳动物生物体中细胞分泌体的组成和动态的全球理解一直缺乏。在这里,我们介绍了一种邻近生物素化策略,其能够在小鼠中以细胞类型选择性方式标记、检测和富集分泌的多肽。我们通过从血浆中直接纯化生物素化的分泌蛋白,生成肝细胞、肌细胞、周细胞和骨髓细胞分泌体的蛋白质组图谱。我们的分泌组数据集验证了已知的细胞类型-蛋白对,揭示了区分细胞类型的分泌多肽,并鉴定了经典血浆蛋白的新细胞来源。最后,我们揭示了一种动态的和以前未描述的肝细胞分泌体的营养依赖性重编程,其特征是细胞溶质酶甜菜碱-同型半胱氨酸S-甲基转移酶 (BHMT) 的非常规分泌增加。这种分泌组谱分析策略使得能够动态和细胞类型特异性地解剖血浆蛋白质组和介导细胞间信号传导的分泌多肽。

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发表时间:2021-03-24
DOI:10.1007/s11033-021-06299-9
作者列表:["Louvrier A","Terranova L","Meyer C","Meyer F","Euvrard E","Kroemer M","Rolin G"]

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