Comprehensive Description of the N-Glycoproteome of Mouse Pancreatic β-Cells and Human Islets
Comprehensive Description of the N-Glycoproteome of Mouse Pancreatic β-Cells and Human Islets
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DOI：
10.1021/pr2007895
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发表时间：
2012-03-01
影响因子：
4.4
通讯作者：
Krek, Wilhelm
中科院分区：
文献类型：
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作者：
Danzer, Carsten;Eckhardt, Katrin;Krek, Wilhelm
细胞表面N-糖蛋白提供了细胞与其环境的关键界面以及用于药物和生物标志物发现的治疗切入点。因此，全面描述它们是一项艰巨的挑战。胰腺的β细胞在血糖稳态中起着至关重要的作用，其功能的破坏有助于糖尿病。通过将细胞表面和全细胞捕获技术与高通量定量蛋白质组学分析相结合，我们报告了从小鼠MIN 6 β细胞和人类胰岛中鉴定出的总共956种独特的N-糖蛋白。这些蛋白质中有349种包含潜在的表面N-糖蛋白，包括孤儿G蛋白偶联受体、新型蛋白酶、受体蛋白激酶和磷酸酶。有趣的是，用葡萄糖和激素GLP 1（已知的胰岛素分泌刺激剂）刺激MIN 6 β细胞，会导致表面N-糖蛋白组表达的显著变化。两者合计，这β-细胞N-糖蛋白质组资源提供了一个全面的看法β-细胞表面蛋白的组成，并扩大了信号系统的范围，可能参与介导β-细胞的各种形式的（病理）生理应激反应和与代谢和激素刺激相关的表面N-糖蛋白表达的动态重塑的程度。此外，它为开发靶向或来源于β细胞表面N-糖蛋白组的糖尿病药物提供了基础。
Cell surface N-glycoproteins provide a key interface of cells to their environment and therapeutic entry points for drug and biomarker discovery. Their comprehensive description denotes therefore a formidable challenge. The beta-cells of the pancreas play a crucial role in blood glucose homeostasis, and disruption of their function contributes to diabetes. By combining cell surface and whole cell capturing technologies with high-throughput quantitative proteomic analysis, we report on the identification of a total of 956 unique N-glycoproteins from mouse MIN6 beta-cells and human islets. Three-hundred-forty-nine of these proteins encompass potential surface N-glycoproteins and include orphan G-protein-coupled receptors, novel proteases, receptor protein kinases, and phosphatases. Interestingly, stimulation of MIN6 beta-cells with glucose and the hormone GLP1, known stimulators of insulin secretion, causes significant changes in surface N-glycoproteome expression. Taken together, this beta-cell N-glycoproteome resource provides a comprehensive view on the composition of beta-cell surface proteins and expands the scope of signaling systems potentially involved in mediating responses of beta-cells to various forms of (patho)physiologic stress and the extent of dynamic remodeling of surface N-glycoprotein expression associated with metabolic and hormonal stimulation. Moreover, it provides a foundation for the development of diabetes medicines that target or are derived from the beta-cell surface N-glycoproteome.