Tetsufumi Ueda Ph.D.
| 5069 BSRB, 109 Zina Pitcher Place, Box 2200 |
| Ann Arbor, MI 48109 |
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This laboratory is concerned with the biochemistry and function of synaptic vesicles. We are currently investigating the mechanism and regulation of glutamate uptake into, and release from, synaptic vesicles in the brain. We are also concerned with its potential role in neuropathophysiology. We have recently isolated a potent, endogenous inhibitory protein which reduces glutamate accumulation into synaptic vesicles. We are studying the physiological role, the mechanism of action, and the mechanism of genesis of this inhibitory protein. In addition, we are engaged in developing potent non-peptide inhibitors of glutamate uptake.
More recently, we have been investigating the role of glucose metabolism on glutamate uptake into and release from synaptic vesicles. We have obtained evidence indicating that ATP produced on the surface of synaptic vesicles by glycolytic enzymes, rather than ATP synthesized in mitochondria, is harnessed for accumulating glutamate into synaptic vesicles.
Ozkan, E.D., Lee, F.S., Ueda, T.: A protein factor that inhibits ATP-dependent glutamate and gamma-aminobutyric acid accumulation into synaptic vesicles: Purification and initial characterization. PNAS USA 94:4137-4142, 1997.
Ozkan, E.D., Ueda, T.: Glutamate transport and storage in synaptic vesicles. Jpn. J. Pharmacol. 77:1-10, 1998.
Lewis, S.M., Ueda, T.: Solubilization and reconstitution of synaptic vesicle glutamate transport system. Meth. Enzymol. 296:125-144, 1998.
Tamura, Y., Ozkan, E.D., Bole, D.G., Ueda, T.: IPF, a vesicular uptake inhibitory protein factor, can reduce the Calcium dependent, evoked release of glutamate, GABA and serotonin. J. Neurochem. 76:1153-64, 2001.
Ogita, K., Hirata, K., Bole, D.G., Yoshida, S., Tamura, Y., Leckenby, A.M., Ueda, T.: Inhibition of vesicular glutamate storage and exocytotic release by Rose Bengal. J. Neurochem. 77:34-42, 2001.
Bole, D.G., Hirata, K., Ueda, T.: Prolonged depolarization of rat cerebral synaptosomes leads to an increase in vesicular glutamate content. Neurosci. Lett. 322:17-20, 2002.
Ikemoto, A., Bole, D.G., Ueda, T.: Glycolysis and glutamate accumulation into synaptic vesicles: Role of glyceraldehyde phosphate dehydrogenase and 3-phosphoglycerate kinase. J. Biol. Chem. 278:5929-5940, 2003.
Ikemoto A., Ueda, T.: Identification of a nerve ending-enriched 29-kDa protein, labeled with [3-32P]1,3-bisphosphoglycerate, as monophosphoglycerate mutase: Inhibition by fructose-2,6-bisphosphate via enhancement of dephosphorylation. J. Neurochem. 85:1382-1393, 2003.
Bole, D.G., Ueda, T.: Inhibition of vesicular glutamate uptake by Rose Bengal-related compounds: Structure-activity relationship. Neurochem. Res. 30:363-369, 2005.
Ueda, T., Ikemoto, A.: Cytoplasmic glycolytic enzymes. Synaptic vesicle-associated glycolytic ATP-generating enzymes: Coupling to neurotransmitter accumulation, in G. Gibson and G. Dienel (eds.), Handbook of Neurochemistry and Molecular Neurobiology, 3rd ed., in Brain Energetics, Cellular and Molecular Integration, Springer, Heidelberg, Germany, vol. 5(chap. 4-1):241-259, 2007.
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