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Comprehensive Description of the N-Glycoproteome of Mouse Pancreatic β-Cells and Human Islets

Author:
Danzer, Carsten, Eckhardt, Katrin, Schmidt, Alexander, Fankhauser, Niklaus, Ribrioux, Sebastien, Wollscheid, Bernd, Müller, Lukas, Schiess, Ralph, Züllig, Richard, Lehmann, Roger, Spinas, Giatgen, Aebersold, Rudolf, Krek, Wilhelm
Source:
Journal of Proteome Research 2012 v.11 no.3 pp. 1598-1608
ISSN:
1535-3907
Subject:
G-protein coupled receptors, biomarkers, diabetes, drugs, glucose, glycoproteins, homeostasis, humans, insulin secretion, islets of Langerhans, mice, protein kinases, proteinases, proteome, proteomics, surface proteins
Abstract:
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 β-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 β-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 β-cells with glucose and the hormone GLP1, known stimulators of insulin secretion, causes significant changes in surface N-glycoproteome expression. Taken together, this β-cell N-glycoproteome resource provides a comprehensive view on the composition of β-cell surface proteins and expands the scope of signaling systems potentially involved in mediating responses of β-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 β-cell surface N-glycoproteome.
Agid:
5681980