How does EFR3 control insulin-stimulated plasma membrane dispersal of GLUT4?

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All cells are surrounded by a structure called the plasma membrane. This provides protection for a cell and helps keep the environment inside the cell stable. The plasma membrane has several functions, including regulating what gets in and out of the cell, and helping the cell sense and respond to external events.Nutrients like sugars are transported across the plasma membrane by specialised proteins called 'transporters'. Understanding how these nutrient transporters are controlled is important, as depending on the conditions a cell may need to increase or decrease the rate of entry of a particular nutrient, perhaps in response to a specific cue.Our group studies how sugar (glucose) transport is regulated, and in particular how this is regulated by a hormone called insulin. Insulin plays an important role in helping keep blood sugar levels constant by controlling the rate by which sugar crosses the plasma membrane of fat and muscle. Defective glucose transport is associated with diseases such as diabetes and also some neurological disorders, hence understanding how transporter proteins are regulated may have considerable impact.Our group has uncovered a new way in which membrane transporters are controlled. We have found that insulin acts to 'disperse' glucose transporters. In the absence of insulin transporters are clustered together (rather like sheep in a pen). Insulin acts to open the gates to the pen and allow the transporters to rapidly move around in the plasma membrane so that they can function effectively and allow glucose transport.We have been able to gain some clues to how a cell does this, and here we seek to further understand how this dispersal is controlled, to ask whether this is specific for sugar transporters or if it is displayed by other nutrient transporters (or happens to all plasma membrane proteins), and we will look to understand how hormones like insulin induce a change in clustering.Our work will, we believe, be of wide interest to colleagues who study cell membrane function from both a basic biology and a translational standpoint. To address these questions, we have created a team of biologists, physicists, and electronics experts to bring their skills to bear on a common problem of fundamental importance.