Expression and characterization of the sugar transporter, Glut 5 in microglial cells of the human and rat brain
Payne-Parrish, Jennifer Ann
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All mammalian cells utilize and metabolize glucose for energy production. Glucose is transported into the cell by members of the family of facilitative glucose transporters, Glut 1-6. Each glucose transporter is cell and tissue specific, and is regulated by either glucose or hormonal stimuli such as insulin. The brain expresses Glut 1-6. Glut 1 is expressed in endothelial cells of the blood brain barrier, Glut 2 is expressed in astrocytes. Glut 3 is expressed in neuronal cells and Glut 4 is expressed in the granule cells of the cerebellum. We have reported that Glut 5 is exclusively expressed in microglial cells in the brain. We were the first to demonstrate the cellular specificity of Glut 5 in the brain. The expression of this transporter in the brain is intriguing. Glut 5 has a very low affinity for glucose, and studies in Xenopus oocytes have shown that Glut 5 functions as a fructose transporter. However, the brain has insignificant concentrations of fructose for transport by Glut 5, and therefore it is unlikely that Glut 5 functions as a fructose transporter in brain. In order to further characterize Glut 5 expression in microglia, the expression pattern, regulation and subcellular localization of Glut 5 were studied in human and rat brain tissue and in cultured cells. These studies demonstrate: that Glut 5 is exclusively expressed in microglia in both human and rat brain. However, Glut 5 is not expressed in all microglial cells; an undefined subset of microglia express Glut 5 in both tissue and in culture. We have also shown that Glut 5 is not a plasma membrane protein but rather is in vesicle-like structures within the cell. In addition we have demonstrated that Glut 5, like other facilitative glucose transporters, can be regulated by glucose concentrations. Finally, levels of Glut 5 appear to be altered in Alzheimer's disease, a condition in which glucose transport and metabolism are affected. In conclusion, the expression of Glut 5 in the brain, an organ with insignificant concentrations of fructose, implies that Glut 5 has an alternate function in the CNS. Our goal was to characterize the cellular expression of Glut 5 in the brain and to determine the factors which regulate Glut 5 expression in these unidentified cells.