Vesicular Glutamate Transporter as Metabolic Regulator.

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Vesicular glutamate transporter (VGLUT) and vesicular inhibitory amino acid transporter (VIAAT) are essential in glutamate- and GABA-mediated chemical transmission, respectively. Using biochemical, cellular biological and molecular biological approaches, we have elucidated structure, function and physiological significance of these transporters. The summaries of the results obtained in the studies are as follows:(1) We revealed topology of VGLUT2.(2) We established in vitro assay system for VGLUT using purified VGLUT and liposome, and revealed some essential amino acid residures for the transport and targeting.(3) We identified essential amino acid residues with purified VIAAT.Actually speaking VIAAT transports beta-alanine.(4) We studied physiological significance of the glutamate signaling in the peripheral tissues using VGLUT1 KO mice. We found that osteoclasts secrete glutamate through transcytosis, and its defect caused osteoporosis.(5) We found strong reversible inhibitors for VGLUT.(6)We identified vesicular nucleotide transporter (VNUT) that is responsible for vesicular storage of ATP. This transporter seems to play a central role in purinergic neurotransmission.