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.
Abstract: Metastatic castration-resistant prostate cancer (mCRPC) is associated with a poor outcome. Prognostic information is useful and aids treatment decisions. However, current nomograms based on clinical parameters alone have weak prognostic accuracy. Therefore, the identification of new prognostic serum biomarkers could be useful.
Abstract: Many parasitic organisms, eukaryotes as well as bacteria, possess surface antigens with amino acid repeats. Making up the interface between host and pathogen such repetitive proteins may be virulence factors involved in immune evasion or cytoadherence. They find immunological applications in serodiagnostics and vaccine development. Here we use proteins which contain perfect repeats as a basis for comparative genomics between parasitic and free-living organisms.
Abstract: Anchoring of proteins to the extracytosolic leaflet of membranes via C-terminal attachment of glycosylphosphatidylinositol (GPI) is ubiquitous and essential in eukaryotes. The signal for GPI-anchoring is confined to the C-terminus of the target protein. In order to identify anchoring signals in silico, we have trained neural networks on known GPI-anchored proteins, systematically optimizing input parameters.
