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

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.