Areas of Interest
Synaptic vesicular glutamate storage and release: mechanism and regulation.
Dr. Ueda's laboratory is engaged in research on the presynaptic aspect of glutamate transmission. In particular, his laboratory has been investigating the glutamate vesicular storage mechanism and its regulation. His group has purified and characterized an inhibitory protein factor (IPF) which blocks vesicular glutamate uptake. His laboratory has also recently discovered a potent, membrane-permeant inhibitor of vesicular glutamate uptake and release; this has potential as a prototype compound developing drugs targeting presynaptic vesicular storage of glutamate. His laboratory is concerned with investigation of various aspects of IPF, the above compound, related compounds, and the glutamate transporter.
In addition, his laboratory is interested in the role of glucose metabolism in synaptic transmission, particularly aspects of glutamate uptake into and release from synaptic vesicles. His laboratory has recently obtained evidence that ATP produced by glycolytic enzymes on the surface of synaptic vesicles, rather than ATP synthesized in mitochondria, plays a major role in harnessing for glutamate accumulation into synaptic vesicles.
- Ikemoto, A. and 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 2003; 85:1382-1393.
- Bole, D.G. and Ueda, T.: Inhibition of vesicular glutamate uptake by Rose Bengal-related compounds: Structure-activity relationship. Neurochem Res 2005; 30:363-369.
- Ueda, T. and 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, 2007;5(chap. 4-1):241-259.
- Winter, H.C. and Ueda, T.: The glutamate uptake system in presynaptic vesicles: Further characterization of structural requirements for inhibitors and substrates. Neurochem Res 2008; 33:223-231.
- Ishida, A., Noda, Y. and Ueda, T.: Synaptic vesicle-bound pyruvate kinase can support vesicular glutamate uptake. Neurochem Res 2009; 34:807-818.
- Özkan, E., Lee, F.S. and Ueda, T.: A protein factor that inhibits ATP-dependent glutamate and g-aminobutyric acid accumulation into synaptic vesicles: purification and initial characterization. Proc Nat Acad Sci USA 1997;94:4137-4142.
- Lewis, S.M., Lee, F.S., Todorova, M., Seyfried, T.N. and Ueda, T.: Synaptic vesicle glutamate uptake in epileptic (EL) mice. Neurochem Int 1997;31:581-585.
- Lewis, S.M. and Ueda, T.: Solubilization and reconstitution of synaptic vesicle glutamate transport system. Meth Enzymol 1998;296:125-144.
- Özkan, E.D. and Ueda, T.: Glutamate transport and storage in synaptic vesicles. Jpn J Pharmacol 1998;77:1-10 (review article).
- Tamura, Y., Özkan , E.D., Bole, D.G. and Ueda, T.: IPF, a vesicular uptake inhibitory protein factor, can reduce the Ca2+-dependent, evoked release of glutamate, GABA and serotonin. J Neurochem 2001;76:1153-64.
- Ogita, K., Hirata, K., Bole, D.G., Yoshida, S., Tamura, Y., Leckenby, A.M. and Ueda, T.: Inhibition of vesicular glutamate storage and exocytotic release by Rose Bengal. J Neurochem 2001;77:34-42.
- Bole, D.G., Hirata, K. and Ueda, T.: Prolonged depolarization of rat cerebral synaptosomes leads to an increase in vesicular glutamate content. Neurosci Lett 2002; 322:17-20.
- Amano, T., Matsubayashi, H., Özkan, E. D., Sasa, M., Serikawa, T. and Ueda, T.: Aberrant reduction of an inhibitory protein factor in a rat epileptic model. Epilepsy Res 2002; 51:81-91.
- Ikemoto, A., Bole, D.G. and Ueda, T.: Glycolysis and glutamate accumulation into synaptic vesicles: Role of glyceraldehyde phosphate dehydrogenase and 3-phosphoglycerate kinase. J Biol Chem 2003; 278:5929-5940.