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A comprehensive description of the N-glycoproteome of mouse pancreatic β-cells and human islets


Danzer, C; Eckhardt, K; Schmidt, A; Fankhauser, N; Ribrioux, S; Wollscheid, B; Müller, L; Schiess, R; Zuellig, R; Lehmann, R; Spinas, G; Aebersold, R; Krek, W (2012). A comprehensive description of the N-glycoproteome of mouse pancreatic β-cells and human islets. Journal of Proteome Research, 11(3):1598-1608.

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, 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.

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, 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:22 Jan 2012 09:49
Last Modified:05 Apr 2016 15:26
Publisher:American Chemical Society
ISSN:1535-3893
Publisher DOI:https://doi.org/10.1021/pr2007895
PubMed ID:22148984

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