Dr. Brent C. Reed's Research Focus

Major Research Interests:
Regulation of insulin receptor and glucose transporter expression.

We study the normal regulation of cellular responses to insulin and how these responses are altered during disease states and their treatment. We are identifying structural domains that confer the characteristic transport kinetics, membrane targeting, and insulin responsiveness that differentiate the behavior of the homologous glucose transporters GLUT1 and GLUT4. Our approach has been to interchange each of several domains of GLUT1 and GLUT4 to form a set of mutant chimeric transporters. Native, chimeric, and truncated transporters are then individually expressed in Xenopus oocytes to determine how their transport properties differ. We have demonstrated that the C-terminal domain not only possesses the property of regulating the distribution of GLUT1 and GLUT4 transporters between intracellular and plasma membrane sites, but also is likely to participate in the regulation of transport activity. The native C-terminal domains of GLUT1 and especially GLUT4 suppress native transporter activity, whereas mutations in the C-terminal domain activate GLUT1 and GLUT4. These observations suggest that this region is a target for transporter regulation by other cellular factors. In pursuing this possibility, we have recently isolated a unique GLUT1 C-terminal binding protein (GLUT1CBP) which contains a PDZ domain that recognizes and binds to the C-terminal four amino acids of GLUT1, and a second domain that interacts with the cellular motor protein myosin VI. These characteristics strongly suggest that GLUT1CBP could provide a protein/vesicle targeting or anchoring role, and we are currently testing that hypothesis.