2018 Vol. 4, No. 6

Cover Story
Insulin secretory granules (ISGs),a group of distinguishing organelles in pancreatic β cells,are responsible for the storage and secretion of insulin to maintain blood glucose homeostasis.The molecular mechanisms of ISG biogenesis,maturation,transportation,and exocytosis are still largely unknown because the proteins involved in these distinct steps have not been fully identified.Subcellular fractionation by density gradient centrifugation has been successfully employed to analyze the proteomes of numerous organelles.However,use of this method to elucidate the ISG proteome is limited by co-fractionated contaminants because ISGs are very dynamic and have abundant exchanges or contacts with other organelles,such as the Golgi apparatus,lysosomes,and endosomes.In this study,the authors developed a new strategy for identifying ISG proteins by protein correlation profiling (PCP)-based proteomics,which included ISG purification by OptiPrep density gradient centrifugation,label-free quantitative proteome,and identification of ISG proteins by correlating fractionation profiles between candidates and known ISG markers.By using this approach,81 ISG proteins were able to be identified.Among them, TM9SF3,a nine-transmembrane protein,was considered a high confidence ISG candidate protein highlighted in the PCP network.Further biochemical and immunofluorescence assays indicated that TM9SF3 localized in ISGs, suggesting that it is a potential new ISG marker.
A critique of the alternating access transporter model of uniport glucose transport
Thermodynamics of voltage-gated ion channels
Electron microscopy combined with spatial analysis: quantitative mapping of the nano-assemblies of plasma membrane-associating proteins and lipids
Proteomic analysis of insulin secretory granules in INS-1 cells by protein correlation profiling
In situ protein micro-crystal fabrication by cryo-FIB for electron diffraction