The role of trafficking regulator of GLUT4 1 (TRARG1) in GLUT4 trafficking

Duan X1, Krycer JR1, Cooke KC1, Yang G1, James DE1,2 and Fazakerley DJ1

  1. Charles Perkins Centre, School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
  2. Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia.

Insulin lowers blood glucose, in part, by enhancing glucose transport into adipose and muscle tissues through the redistribution of glucose transporter GLUT4 from specialised intracellular GLUT4 storage vesicles (GSVs) to the plasma membrane. This process is impaired in insulin resistance, which is a precursor to numerous metabolic disorders including Type 2 diabetes. Trafficking regulator of GLUT4 1 (TRARG1) localises to GSVs and positively regulates GLUT4 trafficking in response to insulin. Understanding how TRARG1 regulates GLUT4 is of interest since lower TRARG1 expression may contribute to impaired GLUT4 trafficking in insulin resistance. To begin to address this we have used a combination of bioinformatics prediction tools and biochemical assays to define the membrane topology of the 173-amino acid mouse TRARG1. This revealed that TRARG1 contains a single transmembrane domain at its C-terminus with a cytosolic N-terminus and extracellular/luminal C-terminus. Interestingly, our studies also revealed a re-entrant loop that also confers TRARG1 membrane association. Based on this model of TRARG1 membrane topology, our current studies are focussed on characterising TRARG1, including identifying the signals that determine its localisation to GSVs, and determining how TRARG1 regulates GLUT4 trafficking.