title: Comprehensive description of the N-glycoproteome of mouse pancreatic β-cells and human islets.
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.
authors.affiliation: Institute of Cell Biology, ETH Zurich , CH-8093 Zurich, Switzerland.
authors.forename: Carsten
authors.initials: C
authors.lastname: Danzer
authors.forename: Katrin
authors.initials: K
authors.lastname: Eckhardt
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmidt
authors.forename: Niklaus
authors.initials: N
authors.lastname: Fankhauser
authors.forename: Sebastien
authors.initials: S
authors.lastname: Ribrioux
authors.forename: Bernd
authors.initials: B
authors.lastname: Wollscheid
authors.forename: Lukas
authors.initials: L
authors.lastname: Müller
authors.forename: Ralph
authors.initials: R
authors.lastname: Schiess
authors.forename: Richard
authors.initials: R
authors.lastname: Züllig
authors.forename: Roger
authors.initials: R
authors.lastname: Lehmann
authors.forename: Giatgen
authors.initials: G
authors.lastname: Spinas
authors.forename: Rudolf
authors.initials: R
authors.lastname: Aebersold
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Krek
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000502:physiology*; D005947:Glucose / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000201:enzymology / Q000378:metabolism*; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D008562:Membrane Glycoproteins; D020543:Proteome; D052216:Glucagon-Like Peptide 1; D020794:Receptor Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; D005947:Glucose