Jonathan S Bogan
Dr. Bogan’s research seeks to understand how glucose uptake is regulated in fat and muscle cells. In these cell types, insulin causes glucose transporters to move from internal membranes to the cell surface. Glucose is then transported into the cells, and is removed from the bloodstream. The regulation of this process is defective in insulin-resistant states such as type 2 diabetes. Dr. Bogan’s laboratory identified regulated proteolytic cleavage as a novel biochemical mechanism to control glucose transporter movement and glucose uptake. Current efforts are focused on characterizing this mechanism in detail, and on determining how this pathway controls metabolism and physiology.
Dr. Bogan’s laboratory studies molecular mechanisms controlling GLUT4 glucose transporter targeting in adipose and muscle cells. In cell types, insulin stimulates glucose uptake by translocating GLUT4 from intracellular membranes to the cell surface. Understanding how this occurs has been a longstanding puzzle. Dr. Bogan and his coworkers identified a protein complex that sequesters GLUT4 in nonendosomal, intracellular vesicles in the absence of insulin. Insulin then acts on this complex to mobilize GLUT4 to the cell surface. This action is coordinated with other insulin signals that act on GTPases to direct vesicle targeting. Current work is directed to understand the biochemical mechanisms involved in this response, including phosphorylation, GTPase signaling, and ubiquitin-like modification pathways.