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Vesicular Glutamate Uptake

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The Glutamate/GABA-Glutamine Cycle

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 13))

Abstract

Glutamate is an excitatory neurotransmitter widely used in the vertebrate central nervous systems. The synaptic transmission process is characterized by three steps: (1) presynaptic vesicular transmitter uptake, (2) presynaptic release, and (3) postsynaptic receptor activation. Presynaptic vesicular glutamate uptake plays an initial pivotal role in glutamate transmission by concentrating glutamate in the vesicular lumen prior to its release. This active glutamate transport harnesses energy derived from ATP hydrolysis, and intra- or extravesicular chloride, and is highly specific to glutamate. The uptake system consists of a vesicular glutamate transporter (VGLUT) and v-type proton-pump ATPase, which generates an electrochemical proton gradient, the driving force of the transport. The major source of ATP is likely to be supplied by glycolytic vesicle-bound enzymes, glyceraldehyde 3-phosphate dehydrogenase, and 3-phosphoglycerate kinase, rather than by mitochondrial ATP synthase. The VGLUT substrate glutamate is proposed to be synthesized by vesicle-bound aspartate amino transferase from α-ketoglutarate, not directly from glutamine. VGLUT has three isoforms, and gaged by their distributions they perform different physiological functions. The mechanism and regulation of vesicular glutamate uptake are discussed. The pharmacology of vesicular glutamate uptake is a developing field of inquiry.

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Abbreviations

AAT:

Aspartate aminotransferase

t-ACPD :

trans-1-amino-1,3-cyclopentanedicarboxylate

CCCP:

Carbonyl cyanide m-chlorophenylhydrazone

CNS:

Central nervous system

FCCP:

Carbonyl cyanide p-trifluoromethoxyphenylhydrazone

GABA:

γ-Amino butyric acid

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

α-KGA:

α-Ketoglutarate

IPF:

Inhibitory protein factor

3-PGK:

3-Phosphoglycerate kinase

VGLUT:

Vesicular glutamate transporter

References

  • Aihara Y, Mashima H, Onda H, Hisano S, Kasuya H, Hori T, Yamada S, Tomura H, Yamada Y, Inoue I, Kojima I, Takeda J (2000) Molecular cloning of a novel brain-type Na+-dependent inorganic phosphate cotransporter. J Neurochem 74:2622–2625

    Article  CAS  PubMed  Google Scholar 

  • Albrecht J, Dolinska M, Hilgier W, Lipkowski AW, Nowacki J (2000) Modulation of glutamine uptake and phosphate-activated glutaminase activity in rat brain mitochondria by amino acids and their synthetic analogues. Neurochem Int 36:341–347

    Article  CAS  PubMed  Google Scholar 

  • Aledo JC, de Pedro E, Gomez-Fabre PM, de Castro IN, Marquez J (1997) Submitochondrial localization and membrane topography of Ehrlich ascitic tumour cell glutaminase. Biochim Biophys Acta 1323:173–184

    Article  CAS  PubMed  Google Scholar 

  • Almqvist J, Huang Y, Laaksonen A, Wang DN, Hovmöller S (2007) Docking and homology modeling explain inhibition of the human vesicular glutamate transporters. Protein Sci 16:1819–1829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Altschuler RA, Neises GR, Harmison GG, Wenthold RJ, Fex J (1981) Immunocytochemical localization of aspartate aminotransferase immunoreactivity in cochlear nucleus of the guinea pig. Proc Natl Acad Sci U S A 78:6553–6657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Altschuler RA, Mosinger JL, Harmison GG, Parakkal MH, Wenthold RJ (1982) Aspartate aminotransferase-like immunoreactivity as a marker for aspartate/glutamate in guinea pig photoreceptors. Nature 298:657–659

    Article  CAS  PubMed  Google Scholar 

  • Amara SG, Fontana ACK (2002) Excitatory amino acid transporters: keeping up with glutamate. Neurochem Int 41:313–318

    Article  CAS  PubMed  Google Scholar 

  • Anderson DC, King SC, Parsons SM (1982) Proton gradient linkage to active uptake of [3H]acetylcholine by Torpedo electric organ synaptic vesicles. Biochemistry 21:3037–3043

    Article  CAS  PubMed  Google Scholar 

  • Araque A, Parpura V, Sanzgiri RP, Haydon PG (1998) Glutamate-dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons. Eur J Neurosci 10:2129–2142

    Article  CAS  PubMed  Google Scholar 

  • Bachelard HS, Cox DW, Drower J (1984) Sensitivity of guinea-pig hippocampal granule cell field potentials to hexoses in vitro: an effect on cell excitability? J Physiol 352:91–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bai L, Xu H, Collins JF, Ghishan FK (2001) Molecular and functional analysis of a novel neuronal vesicular glutamate transporter. J Biol Chem 276:36764–36769

    Article  CAS  PubMed  Google Scholar 

  • Bai L, Zhang X, Ghishan FK (2003) Characterization of vesicular glutamate transporter in pancreatic alpha- and beta- cells and its regulation by glucose. Am J Physiol Gastrointest Liver Physiol 284:G808–G814

    Article  CAS  PubMed  Google Scholar 

  • Bak LK, Zieminnska E, Waagepetersen HS, Schousboe A, Albrecht J (2008) Metabolism of [U-13C] glutamine and [U-13C]glutamate in isolated rat brain mitochondria suggests functional phosphate-activated glutaminase activity in matrix. Neurochem Res 33:273–278

    Article  CAS  PubMed  Google Scholar 

  • Bakker A, Krauss GL, Albert MS, Speck CL, Jones LR, Stark CE, Yassa MA, Bassett SS, Shelton AL, Gallagher M (2012) Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron 74:467–474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Balschun D, Moechars D, Callaerts-Vegh Z, Vermaercke B, Van Acker N, Andries L, D’Hooge R (2010) Vesicular glutamate transporter VGLUT1 has a role in hippocampal long-term potentiation and spatial reversal learning. Cereb Cortex 20:684–693

    Article  PubMed  Google Scholar 

  • Bartlett RD, Esslinger CS, Thompson CM, Bridges RJ (1998) Substituted quinolines as inhibitors of L-glutamate transport into synaptic vesicles. Neuropharmacology 37:839–846

    Article  CAS  PubMed  Google Scholar 

  • Bellocchio EE, Reimer RJ, Fremeau RTJ, Edwards RH (2000) Uptake of glutamate into synaptic vesicles by an inorganic phosphate transporter. Science 289:957–960

    Article  CAS  PubMed  Google Scholar 

  • Benjamin AM, Quastel JH (1972) Locations of amino acids in brain slices from the rat. Biochem J 128:631–646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bennett JP Jr, Mulder AH, Snyder SH (1974) Neurochemical correlates of synaptically active amino acids. Life Sci 15:1045–1056

    Article  CAS  PubMed  Google Scholar 

  • Bergersen LH, Morland C, Ormel L, Rinholm JE, Larsson M, Wold JF, Røe AT, Stranna A, Santello M, Bouvier D, Ottersen OP, Volterra A, Gundersen V (2012) Immunogold detection of L-glutamate and D-serine in small synaptic-like microvesicles in adult hippocampal astrocytes. Cereb Cortex 22:1690–1697

    Article  CAS  PubMed  Google Scholar 

  • Bezzi P, Carmignoto G, Pasti L, Vesce S, Rossi D, Rizzini BL, Pozzan T, Volterra A (1998) Prostaglandins stimulate calcium-dependent glutamate release in astrocytes. Nature 391:281–285

    Article  CAS  PubMed  Google Scholar 

  • Bezzi P, Gundersen V, Galbete JL, Seifert G, Steinhauser C, Pilati E, Volterra A (2004) Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nat Neurosci 7:613–620

    Article  CAS  PubMed  Google Scholar 

  • Billups D, Attwell D (2002) Control of intracellular chloride concentration and GABA response polarity in rat retinal ON-bipolar cells. J Physiol 545:183–198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bisaccia F, Indiveri C, Palmieri F (1985) Purification of reconstitutively active alpha-oxoglutarate carrier from pig heart mitochondria. Biochim Biophys Acta 810:362–369

    Article  CAS  PubMed  Google Scholar 

  • Bloom FE, Ueda T, Battenberg E, Greengard P (1979) Immunocytochemical localization in synapses, of protein I, an endogenous substrate for protein kinases in mammalian brain. Proc Natl Acad Sci U S A 76:5982–5986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bole DG, Ueda T (2005) Inhibition of vesicular uptake by Rose Bengal-related compounds: structure activity relationship. Neurochem Res 30:363–369

    Article  CAS  PubMed  Google Scholar 

  • Bolli R, Nałecz KA, Azzi A (1989) Monocarboxylate and alpha-ketoglutarate carriers from bovine heart mitochondria. Purification by affinity chromatography on immobilized 2-cyano-4-hydroxycinnamate. J Biol Chem 264:18024–18030

    CAS  PubMed  Google Scholar 

  • Boulland JL, Qureshi T, Seal RP, Rafiki A, Gundersen V, Bergersen LH, Fremeau RT Jr, Edwards RH, Storm-Mathisen J, Chaudhry FA (2004) Expression of the vesicular glutamate transporters during development indicates the widespread corelease of multiple neurotransmitters. J Comp Neurol 480:264–280

    Article  CAS  PubMed  Google Scholar 

  • Bradford HF, Ward HK (1976) On glutaminase activity in mammalian synaptosomes. Brain Res 110:115–125

    Article  CAS  PubMed  Google Scholar 

  • Bradford HF, Ward HK, Thomas AJ (1978) Glutamine—a major substrate for nerve endings. J Neurochem 30:1453–1459

    Article  CAS  PubMed  Google Scholar 

  • Brouns I, Pintelon I, Van Genechten J, De Proost I, Timmermans JP, Adriaensen D (2004) Vesicular glutamate transporter 2 is expressed in different nerve fibre populations that selectively contact pulmonary neuroepithelial bodies. Histochem Cell Biol 121:1–12

    Article  CAS  PubMed  Google Scholar 

  • Brumovsky PR (2013) VGLUTs in peripheral neurons and the spinal cord: time for review. ISRN Neurol 829753

    Google Scholar 

  • Brumovsky PR, Robinson DR, La JH, Seroogy KB, Lundgren KH, Albers KM, Kiyatkin ME, Seal RP, Edwards RH, Watanabe M, Hökfelt T, Gebhart GF (2011) Expression of vesicular glutamate transporters type 1 and 2 in sensory and autonomic neurons innervating the mouse colorectum. J Comp Neurol 519:3346–3366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brumovsky PR, Seal RP, Lundgren KH, Seroogy KB, Watanabe M, Gebhart GF (2013) Expression of vesicular glutamate transporters in sensory and autonomic neurons innervating the mouse bladder. J Urol 189:2342–2349

    Article  CAS  PubMed  Google Scholar 

  • Burger PM, Mehl E, Cameron PL, Maycox PR, Baumert M, Lottspeich F, De Camilli P, Jahn R (1989) Synaptic vesicles immunoisolated from rat cerebral cortex contain high levels of glutamate. Neuron 3:715–720

    Article  CAS  PubMed  Google Scholar 

  • Burré J, Beckhaus T, Schägger H, Corvey C, Hofmann S, Karas M, Zimmermann H, Volknandt W (2006) Analysis of the synaptic vesicle proteome using three gel-based protein separation techniques. Proteomics 6:6250–6262

    Article  PubMed  CAS  Google Scholar 

  • Cahoy JD, Emery B, Kaushal A, Foo LC, Zamanian JL, Christopherson KS, Xing Y, Lubischer JL, Krieg PA, Krupenko SA, Thompson WJ, Barres BA (2008) A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci 28:264–278

    Article  CAS  PubMed  Google Scholar 

  • Carlson MD, Ueda T (1990) Accumulated glutamate levels in the synaptic vesicle are not maintained in the absence of active transport. Neurosci Lett 110:325–330

    Article  CAS  PubMed  Google Scholar 

  • Carlson MD, Kish PE, Ueda T (1989) Characterization of the solubilized and reconstituted ATP-dependent vesicular glutamate uptake system. J Biol Chem 264:7369–7376

    CAS  PubMed  Google Scholar 

  • Carty SE, Johnson RG, Scarpa A (1981) Serotonin transport in isolated platelet granules. J Biol Chem 256:11244–11250

    CAS  PubMed  Google Scholar 

  • Casey RP, Njus D, Radda GK, Sehr DA (1977) Active proton uptake by chromaffin granules: observation by amine distribution and phosphorus-31 nuclear magnetic resonance techniques. Biochemistry 16:972–977

    Article  CAS  PubMed  Google Scholar 

  • Cesar M, Hamprecht B (1995) Immunocytochemical examination of neural rat and mouse primary cultures using monoclonal antibodies raised against pyruvate carboxylase. J Neurochem 64:2312–2318

    Article  CAS  PubMed  Google Scholar 

  • Chaudhry FA, Edwards RH, Fonnum F (2008) Vesicular neurotransmitter transporters as targets for endogenous and exogenous toxic substances. Annu Rev Pharmacol Toxicol 48:277–301

    Article  CAS  PubMed  Google Scholar 

  • Cornell-Bell AH, Finkbeiner S, Cooper MS, Smith SJ (1990) Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science 247:470–473

    Article  CAS  PubMed  Google Scholar 

  • Cotman CW, Foster AC, Lanthorn TH (1981) An overview of glutamate as a neurotransmitter. In: Di Chiara G, Gessa GL (eds) Glutamate as a Neurotransmitter. Raven, New York, pp 1–27

    Google Scholar 

  • Cotman CW, Monaghan DT, Ganong AH (1988) Excitatory amino acid neurotransmission: NMDA receptors and Hebb‐type synaptic plasticity. Annu Rev Neurosci 11:61–80

    Article  CAS  PubMed  Google Scholar 

  • Coughenour HD, Spaulding RS, Thompson CM (2004) The synaptic vesicle proteome: a comparative study in membrane protein identification. Proteomics 4:3141–3155

    Article  CAS  PubMed  Google Scholar 

  • Cox DW, Bachelard HS (1982) Attenuation of evoked field potentials from dentate granule cells by low glucose, pyruvate + malate, and sodium fluoride. Brain Res 239:527–534

    Article  CAS  PubMed  Google Scholar 

  • Cox DW, Morris PG, Feeney J, Bachelard HS (1983) 31P n. m. r. studies on cerebral energy metabolism under conditions of hypoglycaemia and hypoxia in vitro. Biochem J 212:365–370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crippa D, Schenk U, Francolini M, Rosa P, Verderio C, Zonta M, Pozzan T, Matteoli M, Carmignoto G (2006) Synaptobrevin2-expressing vesicles in rat astrocytes: insights into molecular characterization, dynamics and exocytosis. J Physiol 570:567–582

    Article  CAS  PubMed  Google Scholar 

  • Curtis DR, Johnston GA (1974) Amino acid transmitters in the mammalian central nervous system. Ergebn Physiol 69:97–188

    CAS  PubMed  Google Scholar 

  • Curtis DR, Phillis JW, Watkins JC (1960) The chemical excitation of spinal neurones by certain acidic amino acids. J Physiol 150:656–682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1–105

    Article  CAS  PubMed  Google Scholar 

  • Dani JW, Chernjavsky A, Smith SJ (1992) Neuronal activity triggers calcium waves in hippocampal astrocyte networks. Neuron 8:429–440

    Article  CAS  PubMed  Google Scholar 

  • Daniels RW, Collins CA, Gelfand MV, Dant J, Brooks ES, Krantz DE, DiAntonio A (2004) Increased expression of the Drosophila vesicular glutamate transporter leads to excess glutamate release and a compensatory decrease in quantal content. J Neurosci 24:10466–10474

    Article  CAS  PubMed  Google Scholar 

  • De Belleroche JS, Bradford HF (1973) Amino acids in synaptic vesicles from mammalian cerebral cortex: a reappraisal. J Neurochem 21:441–451

    Article  PubMed  Google Scholar 

  • De Belleroche JS, Bradford HF (1977) On the site of origin of transmitter amino acids released by depolarization of nerve terminals in vitro. J Neurochem 29:335–343

    Article  PubMed  Google Scholar 

  • de Calignon A, Polydoro M, Suárez-Calvet M, William C, Adamowicz DH, Kopeikina KJ, Pitstick R, Sahara N, Ashe KH, Carlson GA, Spires-Jones TL, Hyman BT (2012) Propagation of tau pathology in a model of early Alzheimer’s disease. Neuron 73:685–697

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • De Camilli P, Harris SM Jr, Huttner WB, Greengard P (1983) Synapsin I (Protein I), a nerve terminal-specific phosphoprotein. II. Its specific association with synaptic vesicles demonstrated by immunocytochemistry in agarose-embedded synaptosomes. J Cell Biol 96:1355–1373

    Article  PubMed  Google Scholar 

  • Dennis SC, Lai JC, Clark JB (1977) Comparative studies on glutamate metabolism in synaptic and non-synaptic rat brain mitochondria. Biochem J 164:727–736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Disbrow JK, Gershten MJ, Ruth JA (1982) Uptake of L-[3H] glutamic acid by crude and purified synaptic vesicles from rat brain. Biochem Biophys Res Commun 108:1221–1227

    Article  CAS  PubMed  Google Scholar 

  • Divito CB, Steece-Collier K, Case DT, Williams SP, Stancati JA, Zhi L, Rubio ME, Sortwell CE, Collier TJ, Sulzer D, Edwards RH, Zhang H, Seal RP (2015) Loss of VGLUT3 produces circadian-dependent hyperdopaminergia and ameliorates motor dysfunction and l-dopa-mediated dyskinesias in a model of Parkinson’s disease. J Neurosci 35:14983–14999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eastwood SL, Harrison PJ (2005) Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons. Schizophr Res 73:159–172

    Article  CAS  PubMed  Google Scholar 

  • Edwards RH (2007) The neurotransmitter cycle and quantal size. Neuron 55:835–858

    Article  CAS  PubMed  Google Scholar 

  • Egebjerg J, Bettler B, Hermans-Borgmeyer I, Heinemann S (1991) Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA. Nature 351:745–774

    Article  CAS  PubMed  Google Scholar 

  • El Mestikawy S, Wallén-Mackenzie A, Fortin GM, Descarries L, Trudeau LE (2011) From glutamate co-release to vesicular synergy: vesicular glutamate transporters. Nat Rev Neurosci 12:204–216

    Article  PubMed  CAS  Google Scholar 

  • Erickson JD, De Gois S, Varoqui H, Schafer MKH, Weihe E (2006) Activity-dependent regulation of vesicular glutamate and GABA transporters: a means to scale quantal size. Neurochem Int 48:643–649

    Article  CAS  PubMed  Google Scholar 

  • Favier M, Carcenac C, Drui G, Boulet S, El Mestikawy S, Savasta M (2013) High-frequency stimulation of the subthalamic nucleus modifies the expression of vesicular glutamate transporters in basal ganglia in a rat model of Parkinson’s disease. BMC Neurosci 14:152

    Article  PubMed  PubMed Central  Google Scholar 

  • Favre-Besse FC, Poirel O, Bersot T, Kim-Grellier E, Daumas S, El Mestikawy S, Acher FC, Pietrancosta N (2014) Design, synthesis and biological evaluation of small-azo-dyes as potent Vesicular Glutamate Transporters inhibitors. Eur J Med Chem 78:236–247

    Article  CAS  PubMed  Google Scholar 

  • Fisher-Bovenkerk C, Kish PE, Ueda T (1988) ATP-dependent glutamate uptake into synaptic vesicles from cerebellar mutant mice. J Neurochem 51:1054–1059

    Article  Google Scholar 

  • Fleck MW, Henze DA, Barrionuevo G, Palmer AM (1993) Aspartate and glutamate mediate excitatory synaptic transmission in area CA1 of the hippocampus. J Neurosci 13:3944–3955

    CAS  PubMed  Google Scholar 

  • Fonnum F, Fykse EM, Roseth S (1998) Uptake of glutamate into synaptic vesicles. Prog Brain Res 116:87–101

    Article  CAS  PubMed  Google Scholar 

  • Franke H, Grummich B, Härtig W, Grosche J, Regenthal R, Edwards RH, Illes P, Krügel U (2006) Changes in purinergic signaling after cerebral injury—involvement of glutamatergic mechanisms? Int J Dev Neurosci 24:123–132

    Article  CAS  PubMed  Google Scholar 

  • Fremeau RT Jr, Troyer MD, Pahner I, Nygaard GO, Tran CH, Reimer RJ, Bellocchio EE, Fortin D, Storm-Mathisen J, Edwards RH (2001) The expression of vesicular glutamate transporters defines two classes of excitatory synapse. Neuron 31:247–260

    Article  CAS  PubMed  Google Scholar 

  • Fremeau RT Jr, Burman J, Qureshi T, Tran CH, Proctor J, Johnson J, Zhang H, Sulzer D, Copenhagen DR, Storm-Mathisen J, Reimer RJ, Chaudhry FA, Edwards RH (2002) The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate. Proc Natl Acad Sci U S A 99:14488–14493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fremeau RT Jr, Voglmaier S, Seal RP, Edwards RH (2004a) VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate. Trends Neurosci 27:98–103

    Article  CAS  PubMed  Google Scholar 

  • Fremeau RT Jr, Kam K, Qureshi T, Johnson J, Copenhagen DR, Storm-Mathisen J, Chaudhry FA, Nicoll RA, Edwards RH (2004b) Vesicular glutamate transporters 1 and 2 target to functionally distinct synaptic release sites. Science 304:1815–1819

    Article  CAS  PubMed  Google Scholar 

  • Fritschy JM (2008) Is my antibody-staining specific? How to deal with pitfalls of immunohistochemistry. Eur J Neurosci 28:2365–2370

    Article  PubMed  Google Scholar 

  • Fyk-Kolodziej B, Dzhagaryan A, Qin P, Pourcho RG (2004) Immunocytochemical localization of three vesicular glutamate transporters in the cat retina. J Comp Neurol 475:518–530

    Article  CAS  PubMed  Google Scholar 

  • Fykse EM, Christensen H, Fonnum F (1989) Comparison of the properties of γ-aminobutyric acid and L-glutamate uptake into synaptic vesicles isolated from rat brain. J Neurochem 52:946–951

    Article  CAS  PubMed  Google Scholar 

  • Goh GY, Huang H, Ullman J, Borre L, Hnasko TS, Trussell LO, Edwards RH (2011) Presynaptic regulation of quantal size: K+/H+ exchange stimulates vesicular glutamate transport. Nat Neurosci 14:1285–1292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Granseth B, Andersson FK, Lindström SH (2015) The initial stage of reversal learning is impaired in mice hemizygous for the vesicular glutamate transporter (VGluT1). Genes Brain Behav 14:477–485

    Article  CAS  PubMed  Google Scholar 

  • Gras C, Herzog E, Bellenchi GC, Bernard V, Ravassard P, Pohl M, Gasnier B, Giros B, El Mestikawy S (2002) A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons. J Neurosci 22:5442–5451

    CAS  PubMed  Google Scholar 

  • Gras C, Vinatier J, Amilhon B, Guerci A, Christov C, Ravassard P, Giros B, El Mestikawy S (2005) Developmentally regulated expression of VGLUT3 during early post-natal life. Neuropharmacology 49:901–911

    Article  CAS  PubMed  Google Scholar 

  • Gras C, Amilhon B, Lepicard EM, Poirel O, Vinatier J, Herbin M, Dumas S, Tzavara ET, Wade MR, Nomikos GG, Hanoun N, Saurini F, Kemel ML, Gasnier B, Giros B, El Mestikawy S (2008) The vesicular glutamate transporter VGLUT3 synergizes striatal acetylcholine tone. Nat Neurosci 11:292–300

    Article  CAS  PubMed  Google Scholar 

  • Graziano A, Liu XB, Murray KD, Jones EG (2008) Vesicular glutamate transporters define two sets of glutamatergic afferents to the somatosensory thalamus and two thalamocortical projections in the mouse. J Comp Neurol 507:1258–1276

    Article  CAS  PubMed  Google Scholar 

  • Greengard P (1976) Possible role for cyclic nucleotides and phosphorylated membrane proteins in postsynaptic actions of neurotransmitters. Nature 260:101–110

    Article  CAS  PubMed  Google Scholar 

  • Grewal S, Defamie N, Zhang X, De Gois S, Shawki A, Mackenzie B, Chen C, Varoqui H, Erickson JD (2009) SNAT2 amino acid transporter is regulated by amino acids of the SLC6 gamma-aminobutyric acid transporter subfamily in neocortical neurons and may play no role in delivering glutamine for glutamatergic transmission. J Biol Chem 284:11224–11236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hackett J, Ueda T (2015) Glutamate release. Neurochem Res 40:2443–2460

    Article  CAS  PubMed  Google Scholar 

  • Hamberger AC, Chiang GH, Nylén ES, Scheff SW, Cotman CW (1979) Glutamate as a CNS transmitter. I. Evaluation of glucose and glutamine as precursors for the synthesis of preferentially released glutamate. Brain Res 168:513–530

    Article  CAS  PubMed  Google Scholar 

  • Hamilton NB, Attwell D (2010) Do astrocytes really exocytose neurotransmitters? Nat Rev Neurosci 11:227–238

    Article  CAS  PubMed  Google Scholar 

  • Harrington EP, Möddel G, Najm IM, Baraban SC (2006) Altered glutamate receptor—transporter expression and spontaneous seizures in rats exposed to methylazoxymethanol in utero. Epilepsia 48:158–168

    Google Scholar 

  • Hartinger J, Jahn R (1993) An anion binding site that regulates the glutamate transporter of synaptic vesicles. J Biol Chem 268:23122–23127

    CAS  PubMed  Google Scholar 

  • Hassinger TD, Atkinson PB, Strecker GJ, Whalen LR, Dudek FE, Kossel AH, Kater SB (1995) Evidence for glutamate-mediated activation of hippocampal neurons by glial calcium waves. J Neurobiol 28:159–170

    Article  CAS  PubMed  Google Scholar 

  • Hayashi M, Otsuka M, Morimoto R, Hirota S, Yatsushiro S, Takeda J, Yamamoto A, Moriyama Y (2001) Differentiation-associated Na+-dependent inorganic phosphate cotransporter (DNPI) is a vesicular glutamate transporter in endocrine glutamatergic systems. J Biol Chem 276:43400–43406

    Article  CAS  PubMed  Google Scholar 

  • Hayashi M, Yamada H, Uehara S, Morimoto R, Muroyama A, Yatsushiro S, Takeda J, Yamamoto A, Moriyama Y (2003) Secretory granule-mediated co-secretion of L-glutamate and glucagon triggers glutamatergic signal transmission in islets of Langerhans. J Biol Chem 278:1966–1974

    Article  CAS  PubMed  Google Scholar 

  • Haydon PG (2001) Glia: listening and talking to the synapse. Nat Rev Neurosci 2:185–193

    Article  CAS  PubMed  Google Scholar 

  • Hell JW, Maycox PR, Jahn R (1990) Energy dependence and functional reconstitution of the gamma-aminobutyric acid carrier from synaptic vesicles. J Biol Chem 265:2111–2117

    CAS  PubMed  Google Scholar 

  • Herman MA, Ackermann F, Trimbuch T, Rosenmund C (2014) Vesicular glutamate transporter expression level affects synaptic vesicle release probability at hippocampal synapses in culture. J Neurosci 34:11781–11791

    Article  CAS  PubMed  Google Scholar 

  • Herring BE, Silm K, Edwards RH, Nicoll RA (2015) Is aspartate an excitatory neurotransmitter? J Neurosci 35:10168–10171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hertz L, Peng L, Dienel GA (2007) Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J Cereb Blood Flow Metab 27:219–249

    Article  CAS  PubMed  Google Scholar 

  • Herzog E, Bellenchi GC, Gras C, Bernard V, Ravassard P, Bedet C, Gasnier B, Giros B, El Mestikawy S (2001) The existence of a second vesicular glutamate transporter specifies subpopulations of glutamatergic neurons. J Neurosci 21:RC181

    CAS  PubMed  Google Scholar 

  • Herzog E, Takamori S, Jahn R, Brose N, Wojcik SM (2006) Synaptic and vesicular co-localization of the glutamate transporters VGLUT1 and VGLUT2 in the mouse hippocampus. J Neurochem 99:1011–1018

    Article  CAS  PubMed  Google Scholar 

  • Hioki H, Fujiyama F, Taki K, Tomioka R, Furuta T, Tamamaki N, Kaneko T (2003) Differential distribution of vesicular glutamate transporters in the rat cerebellar cortex. Neuroscience 117:1–6

    Article  CAS  PubMed  Google Scholar 

  • Hollmann M, O’Shea-Greenfield A, Rogers SW, Heinemann S (1989) Cloning by functional expression of a member of the glutamate receptor family. Nature 342:643–648

    Article  CAS  PubMed  Google Scholar 

  • Holz RW (1978) Evidence that catecholamine transport into chromaffin vesicles is coupled to vesicle membrane potential. Proc Natl Acad Sci U S A 75:5190–5194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hunsberger HC, Rudy CC, Batten SR, Gerhardt GA, Reed MN (2015) P301L tau expression affects glutamate release and clearance in the hippocampal trisynaptic pathway. J Neurochem 132:169–182

    Article  CAS  PubMed  Google Scholar 

  • Ikemoto A, Bole DG, Ueda T (2003) Glycolysis and glutamate accumulation into synaptic vesicles. Role of glyceraldehyde phosphate dehydrogenase and 3-phosphoglycerate kinase. J Biol Chem 278:5929–5940

    Article  CAS  PubMed  Google Scholar 

  • Inta D, Vogt M, Perreau-Lenz S, Schneider M, Pfeiffer N, Wojcik S, Spanagel R, Gass P (2012) Sensorimotor gating, working and social memory deficits in mice with reduced expression of the vesicular glutamate transporter VGLUT1. Behav Brain Res 228:328–332

    Article  CAS  PubMed  Google Scholar 

  • Ishida A, Noda Y, Ueda T (2009) Synaptic vesicle-bound pyruvate kinase can support vesicular glutamate uptake. Neurochem Res 34:807–818

    Article  CAS  PubMed  Google Scholar 

  • Jeftinija SD, Jeftinija KV, Stefanovic G, Liu F (1996) Neuroligand-evoked calcium-dependent release of excitatory amino acids from cultured astrocytes. J Neurochem 66:676–684

    Article  CAS  PubMed  Google Scholar 

  • Johnson RG Jr (1988) Accumulation of biological amines into chromaffin granules: a model for hormone and neurotransmitter transport. Physiol Rev 68:232–307

    CAS  PubMed  Google Scholar 

  • Johnson RG, Scarpa A (1979) Protonmotive force and catecholamine transport in isolated chromaffin granules. J Biol Chem 254:3750–3760

    CAS  PubMed  Google Scholar 

  • Johnson RG, Pfister D, Carty SE, Scarpa A (1979) Biological amine transport in chromaffin ghosts. J Biol Chem 254:10963–10972

    CAS  PubMed  Google Scholar 

  • Johnson J, Tian N, Caywood MS, Reimer RJ, Edwards RH, Copenhagen DR (2003) Vesicular neurotransmitter transporter expression in developing postnatal rodent retina: GABA and glycine precede glutamate. J Neurosci 23:518–529

    CAS  PubMed  Google Scholar 

  • Jourdain P, Bergersen LH, Bhaukaurally K, Bezzi P, Santello M, Domercq M, Matute C, Tonello F, Gundersen V, Volterra A (2007) Glutamate exocytosis from astrocytes controls synaptic strength. Nat Neurosci 10:331–339

    Article  CAS  PubMed  Google Scholar 

  • Juge N, Yoshida Y, Yatsushiro S, Omote H, Moriyama Y (2006) Vesicular glutamate transporter contains two independent transport machineries. J Biol Chem 281:39499–39506

    Article  CAS  PubMed  Google Scholar 

  • Juge N, Gray JA, Omote H, Miyaji T, Inoue T, Hara C, Uneyama H, Edwards RH, Nicoll RA, Moriyama Y (2010) Metabolic control of vesicular glutamate transport and release. Neuron 68:99–112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kam K, Nicoll R (2007) Excitatory synaptic transmission persists independently of the glutamate–glutamine cycle. J Neurosci 27:9192–9200

    Article  CAS  PubMed  Google Scholar 

  • Kaneko T, Fujiyama F (2002) Complementary distribution of vesicular glutamate transporters in the central nervous system. Neurosci Res 42:243–250

    Article  CAS  PubMed  Google Scholar 

  • Kang T-C, Kim D-S, Kwak S-E, Kim J-E, Kim DW, Kang JH, Won MH, Kwon O-S, Choi S-Y (2005) Valproic acid reduces enhanced vesicular glutamate transporter immunoreactivities in the dentate gyrus of the seizure prone gerbil. Neuropharmacology 49:912–921

    Article  CAS  PubMed  Google Scholar 

  • Kanner BI, Sharon I (1978) Active transport of L-glutamate by membrane vesicles isolated from rat brain. Biochemistry 17:3949–3953

    Article  CAS  PubMed  Google Scholar 

  • Kashani A, Betancur C, Giros B, Hirsch E, Mestikawy S (2007) Altered expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in Parkinson disease. Neurobiol Aging 28:568–578

    Article  CAS  PubMed  Google Scholar 

  • Kashani A, Lepicard E, Poirel O, Videau C, David JP, Fallet-Bianco C, Simon A, Delacourte A, Giros B, Epelbaum J, Betancur C, El Mestikawy S (2008) Loss of VGLUT1 and VGLUT2 in the prefrontal cortex is correlated with cognitive decline in Alzheimer disease. Neurobiol Aging 29:1619–1630

    Article  CAS  PubMed  Google Scholar 

  • Kim DS, Kwak SE, Kim JE, Won MH, Choi HC, Song HK, Kwon OS, Kim YI, Choi SY, Kang TC (2005) Bilateral enhancement of excitation via up-regulation of vesicular glutamate transporter subtype 1, not subtype 2, immunoreactivity in the unilateral hypoxic epilepsy model. Brain Res 1055:122–130

    Article  CAS  PubMed  Google Scholar 

  • Kim JE, Kim DS, Kwak SE, Choi HC, Song HK, Choi SY, Kwon OS, Kim YI, Kang TC (2007) Anti-glutamatergic effect of riluzole: comparison with valproic acid. Neuroscience 147:136–145

    Article  CAS  PubMed  Google Scholar 

  • Kish PE, Fischer-Bovenkerk C, Ueda T (1989) Active transport of gamma-aminobutyric acid and glycine into synaptic vesicles. Proc Natl Acad Sci U S A 86:3877–3881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kontro P, Marnela KM, Oja SS (1980) Free amino acids in the synaptosome and synaptic vesicle fractions of different bovine brain areas. Brain Res 184:129–141

    Article  CAS  PubMed  Google Scholar 

  • Kraus T, Neuhuber WL, Raab M (2004) Vesicular glutamate transporter 1 immunoreactivity in motor endplates of striated esophageal but not skeletal muscles in the mouse. Neurosci Lett 360:53–56

    Article  CAS  PubMed  Google Scholar 

  • Kvamme E, Torgner IA, Roberg B (1991) Evidence indicating that pig renal phosphate-activated glutaminase has a functionally predominant external localization in the inner mitochondrial membrane. J Biol Chem 266:13185–13192

    CAS  PubMed  Google Scholar 

  • Landry M, Bouali-Benazzouz R, El Mestikawy S, Ravassard P, Nagy F (2004) Expression of vesicular glutamate transporters in rat lumbar spinal cord, with a note on dorsal root ganglia. J Comp Neurol 468:380–394

    Article  CAS  PubMed  Google Scholar 

  • Leo S, Moechars D, Callaerts-Vegh Z, D’Hooge R, Meert T (2009) Impairment of VGLUT2 but not VGLUT1 signaling reduces neuropathy-induced hypersensitivity. Eur J Pain 13:1008–1017

    Article  CAS  PubMed  Google Scholar 

  • Lewis SM, Lee FS, Todorova M, Seyfried TN, Ueda T (1997) Synaptic vesicle glutamate uptake in epileptic (EL) mice. Neurochem Int 31:581–585

    Article  CAS  PubMed  Google Scholar 

  • Li JL, Fujiyama F, Kaneko T, Mizuno N (2003) Expression of vesicular glutamate transporters, VGluT1 and VGluT2, in axon terminals of nociceptive primary afferent fibers in the superficial layers of the medullary and spinal dorsal horns of the rat. J Comp Neurol 457:236–249

    Article  CAS  PubMed  Google Scholar 

  • Li D, Ropert N, Koulakoff A, Giaume C, Oheim M (2008) Lysosomes are the major vesicular compartment undergoing Ca2+-regulated exocytosis from cortical astrocytes. J Neurosci 28:7648–7658

    Article  CAS  PubMed  Google Scholar 

  • Li D, Hérault K, Silm K, Evrard A, Wojcik S, Oheim M, Herzog E, Ropert N (2013) Lack of evidence for vesicular glutamate transporter expression in mouse astrocytes. J Neurosci 33:4434–4455

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Abdel Samad O, Zhang L, Duan B, Tong Q, Lopes C, Ji RR, Lowell BB, Ma Q (2010) VGLUT2-dependent glutamate release from nociceptors is required to sense pain and suppress itch. Neuron 68:543–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Logan WJ, Snyder SH (1972) High affinity uptake systems for glycine, glutamic and aspartic acids in synaptosomes of rat central nervous tissues. Brain Res 42:413–431

    Article  CAS  PubMed  Google Scholar 

  • Lou S, Duan B, Vong L, Lowell BB, Ma Q (2013) Runx1 controls terminal morphology and mechanosensitivity of VGLUT3-expressing C-mechanoreceptors. J Neurosci 33:870–882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lussier AL, Romay-Tallón R, Caruncho HJ, Kalynchuk LE (2013) Altered GABAergic and glutamatergic activity within the rat hippocampus and amygdala in rats subjected to repeated corticosterone administration but not restraint stress. Neuroscience 231:38–48

    Article  CAS  PubMed  Google Scholar 

  • Ma Q (2014) Itch modulation by VGLUT2-dependent glutamate release from somatic sensory neurons. In: Carstens E, Akiyama T (eds) Itch: mechanisms and treatment. CRC Press, Boca Raton, Chapter 21, Frontiers in Neuroscience

    Google Scholar 

  • Mancini GM, de Jonge HR, Galjaard H, Verheijen FW (1989) Characterization of a proton-driven carrier for sialic acid in the lysosomal membrane. Evidence for a group-specific transport system for acidic monosaccharides. J Biol Chem 264:15247–15254

    CAS  PubMed  Google Scholar 

  • Mangan JL, Whittaker VP (1966) The distribution of free amino acids in subcellular fractions of guinea-pig brain. Biochem J 98:128–137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marchaland J, Calì C, Voglmaier SM, Li H, Regazzi R, Edwards RH, Bezzi P (2008) Fast subplasma membrane Ca2-transients control exoendocytosis of synaptic-like microvesicles in astrocytes. J Neurosci 28:9122–9132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martinez-Hernandez A, Bell KP, Norenberg MD (1977) Glutamine synthetase: glial localization in brain. Science 195:1356–1358

    Article  CAS  PubMed  Google Scholar 

  • Masson J, Darmon M, Conjard A, Chuhma N, Ropert N, Thoby-Brisson M, Foutz AS, Parrot S, Miller GM, Jorisch R, Polan J, Hamon M, Hen R, Rayport S (2006) Mice lacking brain/kidney phosphate-activated glutaminase have impaired glutamatergic synaptic transmission, altered breathing, disorganized goal-directed behavior and die shortly after birth. J Neurosci 26:4660–4671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Masu M, Tanabe Y, Tsuchida K, Shigemoto R, Nakanishi S (1991) Sequence and expression of a metabotropic glutamate receptor. Nature 349:760–765

    Article  CAS  PubMed  Google Scholar 

  • Maycox PR, Deckwerth T, Hell JW, Jahn R (1988) Glutamate uptake by brain synaptic vesicles. Energy dependence of transport and functional reconstitution in proteoliposomes. J Biol Chem 263:15423–15428

    CAS  PubMed  Google Scholar 

  • Maycox PR, Hell JW, Jahn R (1990) Amino acid neurotransmission: spotlight on synaptic vesicles. Trends Neurosci 13:83–87

    Article  CAS  PubMed  Google Scholar 

  • McKenna MC (2007) The glutamate–glutamine cycle Is not stoichiometric: fates of glutamate in brain. J Neurosci Res 85:3347–3358

    Article  CAS  PubMed  Google Scholar 

  • McKenna MC, Tildon JT, Stevenson JH, Boatright R, Huang S (1993) Regulation of energy metabolism in synaptic terminals and cultured rat brain astrocytes: differences revealed using aminooxyacetate. Dev Neurosci 15:320–329

    Article  CAS  PubMed  Google Scholar 

  • McKenna MC, Stevenson JH, Huan X, Hopkins IB (2000) Differential distribution of the enzymes glutamate dehydrogenase and aspartate aminotransferase in cortical synaptic mitochondria contributes to metabolic compartmentation in cortical synaptic terminals. Neurochem Int 37:229–241

    Article  CAS  PubMed  Google Scholar 

  • McMahon HT, Nicholls DG (1991) The bioenergetics of neurotransmitter release. Biochim Biophys Acta 1059:243–264

    Article  CAS  PubMed  Google Scholar 

  • Miller SL, Fenstermacher E, Bates J, Blacker D, Sperling RA, Dickerson BC (2008) Hippocampal activation in adults with mild cognitive impairment predicts subsequent cognitive decline. J Neurol Neurosurg Psychiatry 79:630–635

    Article  CAS  PubMed  Google Scholar 

  • Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191:144–148

    Article  CAS  PubMed  Google Scholar 

  • Mitchell P (1966) Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. Biol Rev Camb Philos Soc 41:445–502

    Article  CAS  PubMed  Google Scholar 

  • Miyaji T, Echigo N, Hiasa M, Senoh S, Omote H, Moriyama Y (2008) Identification of a vesicular aspartate transporter. Proc Natl Acad Sci U S A 105:11720–11724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyazaki T, Fukaya M, Shimizu H, Watanabe M (2003) Subtype switching of vesicular glutamate transporters at parallel fibre-Purkinje cell synapses in developing mouse cerebellum. Eur J Neurosci 17:2563–2572

    Article  PubMed  Google Scholar 

  • Moechars D, Weston MC, Leo S, Callaerts-Vegh Z, Goris I, Daneels G, Buist A, Cik M, van der Spek P, Kass S, Meert T, D’Hooge R, Rosenmund C, Hampson RM (2006) Vesicular glutamate transporter VGLUT2 expression levels control quantal size and neuropathic pain. J Neurosci 26:12055–12066

    Article  CAS  PubMed  Google Scholar 

  • Monaghan DT, Bridges RJ, Cotman CW (1989) The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system. Annu Rev Pharmacol Toxicol 29:365–402

    Article  CAS  PubMed  Google Scholar 

  • Montana V, Ni Y, Sunjara V, Hua X, Parpura V (2004) Vesicular glutamate transporter-dependent glutamate release from astrocytes. J Neurosci 24:2633–2642

    Article  CAS  PubMed  Google Scholar 

  • Morimoto R, Hayashi M, Yatsushiro S, Otsuka M, Yamamoto A, Moriyama Y (2003) Co-expression of vesicular glutamate transporters (VGLUT1 and VGLUT2) and their association with synaptic-like microvesicles in rat pinealocytes. J Neurochem 84:382–391

    Article  CAS  PubMed  Google Scholar 

  • Morimoto R, Uehara S, Yatsushiro S, Juge N, Hua Z, Senoh S, Echigo N, Hayashi M, Mizoguchi T, Ninomiya T, Udagawa N, Omote H, Yamamoto A, Edwards RH, Moriyama Y (2006) Secretion of L-glutamate from osteoclasts through transcytosis. EMBO J 25:4175–4186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moriyama Y, Yamamoto A (1995) Vesicular L-glutamate transporter in microvesicles from bovine pineal glands. Driving force, mechanism of chloride anion activation, and substrate specificity. J. Biol Chem 270:22314–22320

    Article  CAS  Google Scholar 

  • Moriyoshi K, Masu M, Ishii T, Shigemoto R, Mizuno N, Nakanishi S (1991) Molecular cloning and characterization of the rat NMDA receptor. Nature 354:31–37

    Article  CAS  PubMed  Google Scholar 

  • Morken TS, Brekke E, Håberg A, Widerøe M, Brubakk AM, Sonnewald U (2014) Neuron-astrocyte interactions, pyruvate carboxylation and the pentose phosphate pathway in the neonatal rat brain. Neurochem Res 39:556–569

    Article  CAS  PubMed  Google Scholar 

  • Mothet JP, Pollegioni L, Ouanounou G, Martineau M, Fossier P, Baux G (2005) Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine. Proc Natl Acad Sci U S A 102:5606–5611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nadler JV, Vaca KW, White WF, Lynch GS, Cotman CW (1976) Aspartate and glutamate as possible transmitters of excitatory hippocampal afferents. Nature 260:538–540

    Article  CAS  PubMed  Google Scholar 

  • Nadler JV, White WF, Vaca KW, Perry BW, Cotman CW (1978) Biochemical correlates of transmission mediated by glutamate and aspartate. J Neurochem 31:147–155

    Article  CAS  PubMed  Google Scholar 

  • Naito S, Ueda T (1981) Affinity-purified anti-protein I antibody. Specific inhibitor of phosphorylation of protein I, a synaptic protein. J Biol Chem 256:10657–10663

    CAS  PubMed  Google Scholar 

  • Naito S, Ueda T (1982) ATP-dependent glutamate uptake into Protein I-associated synaptic vesicles. Soc Neurosci Abst 8:878

    Google Scholar 

  • Naito S, Ueda T (1983) Adenosine triphosphate-dependent uptake of glutamate into protein I-associated synaptic vesicles. J Biol Chem 258:696–699

    CAS  PubMed  Google Scholar 

  • Naito S, Ueda T (1985) Characterization of glutamate uptake into synaptic vesicles. J Neurochem 44:99–109

    Article  CAS  PubMed  Google Scholar 

  • Nakamura K, Hioki H, Fujiyama F, Kaneko T (2005) Postnatal changes of vesicular glutamate transporter (VGluT)1 and VGluT2 immunoreactivities and their colocalization in the mouse forebrain. J Comp Neurol 492:263–288

    Article  CAS  PubMed  Google Scholar 

  • Neale SA, Copeland CS, Uebele VN, Thomson FJ, Salt TE (2013) Modulation of hippocampal synaptic transmission by the kynurenine pathway member xanthurenic acid and other VGLUT inhibitors. Neuropsychopharmacology 38:1060–1067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neale SA, Copeland CS, Salt TE (2014) Effect of VGLUT inhibitors on glutamatergic synaptic transmission in the rodent hippocampus and prefrontal cortex. Neurochem Int 73:159–165

    Article  CAS  PubMed  Google Scholar 

  • Newman EA, Zahs KR (1998) Modulation of neuronal activity by glial cells in the retina. J Neurosci 18:4022–4028

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ni Y, Parpura V (2009) Dual regulation of Ca2+-dependent glutamate release from astrocytes: vesicular glutamate transporters and cytosolic glutamate levels. Glia 57:1296–1305

    Article  PubMed  PubMed Central  Google Scholar 

  • Ni B, Rosteck PR Jr, Nadi NS, Paul SM (1994) Cloning and expression of a cDNA encoding a brain-specific Na+-dependent inorganic phosphate cotransporter. Proc Natl Acad Sci U S A 91:5607–5611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nicholls D, Attwell D (1990) The release and uptake of excitatory amino acids. Trends Pharmacol Sci 11:462–468

    Article  PubMed  Google Scholar 

  • Nicholls DG, Sihra TS (1986) Synaptosomes possess an exocytotic pool of glutamate. Nature 321:772–773

    Article  CAS  PubMed  Google Scholar 

  • Njus D, Kelley PM, Harnadek GJ (1986) Bioenergetics of secretary vesicles. Biochim Biophys Acta 853:237–265

    Article  CAS  PubMed  Google Scholar 

  • Ogita K, Hirata K, Bole DG, Yoshida S, Tamura Y, Leckenby AM, Ueda T (2001) Inhibition of vesicular glutamate storage and exocytotic release by Rose Bengal. J Neurochem 77:34–42

    Article  CAS  PubMed  Google Scholar 

  • Oliveira AL, Hydling F, Olsson E, Shi T, Edwards RH, Fujiyama F, Kaneko T, Hökfelt T, Cullheim S, Meister B (2003) Cellular localization of three vesicular glutamate transporter mRNAs and proteins in rat spinal cord and dorsal root ganglia. Synapse 50:117–129

    Article  CAS  PubMed  Google Scholar 

  • Omote H, Miyaji T, Juge N, Moriyama Y (2011) Vesicular neurotransmitter transporter: bioenergetics and regulation of glutamate transport. Biochemistry 50:5558–5565

    Article  CAS  PubMed  Google Scholar 

  • Ormel L, Stensrud MJ, Chaudhry FA, Gundersen V (2012a) A distinct set of synaptic-like microvesicles in atroglial cells contain VGLUT3. Glia 60:1289–1300

    Article  PubMed  Google Scholar 

  • Ormel L, Stensrud MJ, Bergersen LH, Gundersen V (2012b) VGLUT1 is localized in astrocytic processes in several brain regions. Glia 60:229–238

    Article  PubMed  Google Scholar 

  • Ozkan ED, Ueda T (1998) Glutamate transport and storage in synaptic vesicles. Jpn J Pharmacol 77:1–10

    Article  CAS  PubMed  Google Scholar 

  • Özkan ED, Lee FS, Ueda T (1997) A protein factor that inhibits ATP-dependent glutamate and γ-aminobutyric acid accumulation into synaptic vesicles: purification and initial characterization. Proc Natl Acad Sci U S A 94:4137–4142

    Article  PubMed  PubMed Central  Google Scholar 

  • Palaiologos G, Hertz L, Schousboe A (1988) Evidence that aspartate aminotransferase activity and ketodicarboxylate carrier function are essential for biosynthesis of transmitter glutamate. J Neurochem 51:317–320

    Article  CAS  PubMed  Google Scholar 

  • Parpura V, Haydon PG (2000) Physiological astrocytic calcium levels stimulate glutamate release to modulate adjacent neurons. Proc Natl Acad Sci U S A 97:8629–8634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG (1994) Glutamate-mediated astrocyte-neuron signalling. Nature 369:744–747

    Article  CAS  PubMed  Google Scholar 

  • Parsons SM, Prior C, Marshall IG (1993) Acetylcholine transport, storage, and release. Int Rev Neurobiol 35:279–390

    Article  CAS  PubMed  Google Scholar 

  • Pasti L, Volterra A, Pozzan T, Carmignoto G (1997) Intracellular calcium oscillations in astrocytes: a highly plastic, bidirectional form of communication between neurons and astrocytes in situ. J Neurosci 17:7817–7830

    CAS  PubMed  Google Scholar 

  • Patel MS (1974) The relative significance of CO2-fixing enzymes in the metabolism of rat brain. J Neurochem 22:717–724

    Article  CAS  PubMed  Google Scholar 

  • Patel SA, Nagy JO, Bolstad ED, Gerdes JM, Thompson CM (2007) Tetrapeptide inhibitors of the glutamate vesicular transporter (VGLUT). Bioorg Med Chem Lett 17:5125–5128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Persson S, Boulland JL, Aspling M, Larsson M, Fremeau RT Jr, Edwards RH, Storm-Mathisen J, Chaudhry FA, Broman J (2006) Distribution of vesicular glutamate transporters 1 and 2 in the rat spinal cord, with a note on the spinocervical tract. J Comp Neurol 497:683–701

    Article  CAS  PubMed  Google Scholar 

  • Pflibsen L, Stang KA, Sconce MD, Wilson VB, Hood RL, Meshul CK, Mitchell SH (2015) Executive function deficits and glutamatergic protein alterations in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. J Neurosci Res 93:1849–1864

    Article  CAS  PubMed  Google Scholar 

  • Phillips JH, Allison YP (1978) Proton translocation of the bovine chromaffin-granule membrane. Biochem J 170:661–672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pietrancosta N, Kessler A, Favre-Besse FC, Triballeau N, Quentin T, El Mestikawy S, Acher FC (2010) Rose Bengal analogs and vesicular glutamate transporters (VGLUTs). Bioorg Med Chem 18:6922–6933

    Article  CAS  PubMed  Google Scholar 

  • Platel JC, Dave KA, Gordon V, Lacar B, Rubio ME, Bordey A (2010) NMDA receptors activated by subventricular zone astrocytic glutamate are critical for neuroblast survival prior to entering a synaptic network. Neuron 65:859–872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Porter JT, McCarthy KD (1996) Hippocampal astrocytes in situ respond to glutamate released from synaptic terminals. J Neurosci 16:5073–5081

    CAS  PubMed  Google Scholar 

  • Preobraschenski J, Zander JF, Suzuki T, Ahnert-Hilger G, Jahn R (2014) Vesicular glutamate transporters use flexible anion and cation binding sites for efficient accumulation of neurotransmitter. Neuron 84:1287–1301

    Article  CAS  PubMed  Google Scholar 

  • Price GD, Trussell LO (2006) Estimate of the chloride concentration in a central glutamatergic terminal: a gramicidin perforated-patch study on the calyx of Held. J Neurosci 26:11432–11436

    Article  CAS  PubMed  Google Scholar 

  • Putcha D, Brickhouse M, O’Keefe K, Sullivan C, Rentz D, Marshall G, Dickerson B, Sperling R (2011) Hippocampal hyperactivation associated with cortical thinning in Alzheimer’s disease signature regions in non-demented elderly adults. J Neurosci 31:17680–17688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raju DV, Ahern TH, Shah DJ, Wright TM, Standaert DG, Hall RA, Smith Y (2008) Differential synaptic plasticity of the corticostriatal and thalamostriatal systems in an MPTP-treated monkey model of parkinsonism. Eur J Neurosci 27:1647–1658

    Article  PubMed  Google Scholar 

  • Rassin DK (1972) Amino acids as putative transmitters: failure to bind to synaptic vesicles of guinea pig cerebral cortex. J Neurochem 19:139–148

    Article  CAS  PubMed  Google Scholar 

  • Reid RA, Moyle J, Mitchell P (1966) Synthesis of adenosine triphosphate by a protonmotive force in rat liver mitochondria. Nature 212:257–258

    Article  CAS  PubMed  Google Scholar 

  • Reimer RJ, Edwards RH (2004) Organic anion transport is the primary function of the SLC17/type I phosphate transporter family. Pflugers Arch 447:629–635

    Article  CAS  PubMed  Google Scholar 

  • Reis M, Farage M, Wolosker H (2000) Chloride-dependent inhibition of vesicular glutamate uptake by alpha-keto acids accumulated in maple syrup urine disease. Biochim Biophys Acta 1475:114–118

    Article  CAS  PubMed  Google Scholar 

  • Roberg B, Torgner IA, Kvamme E (1995) The orientation of phosphate activated glutaminase in the inner mitochondrial membrane of synaptic and non-synaptic rat brain mitochondria. Neurochem Int 27:367–376

    Article  CAS  PubMed  Google Scholar 

  • Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, Gerstein H, Yu GQ, Mucke L (2007) Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model. Science 316:750–754

    Article  CAS  PubMed  Google Scholar 

  • Roberson ED, Halabisky B, Yoo JW, Yao J, Chin J, Yan F, Wu T, Hamto P, Devidze N, Yu GQ, Palop JJ, Noebels JL, Mucke L (2011) Amyloid-β/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer’s disease. J Neurosci 31:700–711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rogoz K, Lagerström MC, Dufour S, Kullander K (2012) VGLUT2-dependent glutamatergic transmission in primary afferents is required for intact nociception in both acute and persistent pain modalities. Pain 153:1525–1536

    Article  CAS  PubMed  Google Scholar 

  • Roseth S, Fykse EM, Fonnum F (1995) Uptake of L-glutamate into rat brain synaptic vesicles: effect of inhibitors that bind specifically to the glutamate transporter. J Neurochem 65:96–103

    Article  CAS  PubMed  Google Scholar 

  • Roseth S, Fykse EM, Fonnum F (1998) Uptake of L-glutamate into synaptic vesicles: competitive inhibition by dyes with biphenyl and amino and sulphonic acid substituted naphthyl groups. Biochem Pharmacol 56:1243–1249

    Article  CAS  PubMed  Google Scholar 

  • Ruel J, Emery S, Nouvian R, Bersot T, Amilhon B, Van Rybroek JM, Rebillard G, Lenoir M, Eybalin M, Delprat B, Sivakumaran TA, Giros B, El Mestikawy S, Moser T, Smith RJ, Lesperance MM, Puel JL (2008) Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice. Am J Hum Genet 83:278–292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schafer MK-H, Varoqui H, Defamie N, Weihe E, Erickson JD (2002) Molecular cloning and functional identification of mouse vesicular glutamate transporter 3 and its expression in subsets of novel excitatory neurons. J Biol Chem 277:50734–50748

    Article  PubMed  Google Scholar 

  • Schenck S, Wojcik SM, Brose N, Takamori S (2009) A chloride conductance in VGLUT1 underlies maximal glutamate loading into synaptic vesicles. Nat Neurosci 12:156–162

    Article  CAS  PubMed  Google Scholar 

  • Schousboe A, Hertz L (1981) Role of astroglial cells in glutamate homeostasis. In: Di Chiara G, Gessa GL (eds) Glutamate as a neurotransmitter. Raven Press, New York, pp 103–113

    Google Scholar 

  • Schousboe A, Westergaard N, Waagepetersen H, Larsson OM, Bakken IJ, Sonnewald U (1997) Trafficking between glia and neurons of TCA cycle intermediates and related metabolites. Glia 21:99–105

    Article  CAS  PubMed  Google Scholar 

  • Seal RP, Akil O, Yi E, Weber CM, Grant L, Yoo J, Clause A, Kandler K, Noebels JL, Glowatzki E, Lusting LR, Edwards RH (2008) Sensorineural deafness and seizures in mice lacking vesicular glutamate transporter 3. Neuron 57:263–275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seal RP, Wang X, Guan Y, Raja SN, Woodbury CJ, Basbaum AI, Edwards RH (2009) Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors. Nature 462:651–655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Serres S, Raffard G, Franconi JM, Merle M (2008) Close coupling between astrocytic and neuronal metabolisms to fulfill anaplerotic and energy needs in the rat brain. J Cereb Blood Flow Metab 28:712–724

    Article  CAS  PubMed  Google Scholar 

  • Shank RP, Aprison MH (1988) Glutamate as a neurotransmitter. In: Kvamme E (ed) Glutamine and Glutamate in Mammals, vol II. CRC Press, Boca Raton, pp 3–20

    Google Scholar 

  • Shank RP, Campbell GL (1981) Avid Na+-dependent high-affinity uptake of alpha-ketoglutarate by nerve terminal enriched material from mouse cerebellum. Life Sci 28:843–850

    Article  CAS  PubMed  Google Scholar 

  • Shank RP, Campbell GL (1982) Glutamine and alpha-ketoglutarate uptake and metabolism by nerve terminals enriched material from mouse cerebellum. Neurochem Res 7:601–616

    Article  CAS  PubMed  Google Scholar 

  • Shank RP, Campbell GL (1984) Alpha-ketoglutarate and malate uptake and metabolism by synaptosomes: further evidence for an astrocyte-to-neuron metabolic shuttle. J Neurochem 42:1153–1161

    Article  CAS  PubMed  Google Scholar 

  • Shank RP, Bennett GS, Freytag SO, Campbell GL (1985) Pyruvate carboxylase: astrocyte-specific enzyme implicated in the replenishment of amino acid neurotransmitter pools. Brain Res 329:364–367

    Article  CAS  PubMed  Google Scholar 

  • Shank RP, Leo GC, Zielke HR (1993) Cerebral metabolic compartmentation as revealed by nuclear magnetic resonance analysis of D-[1-13C]glucose metabolism. J Neurochem 61:315–323

    Article  CAS  PubMed  Google Scholar 

  • Shapiro RA, Haser WG, Curthoys NP (1985) The orientation of phosphate-dependent glutaminase on the inner membrane of rat renal mitochondria. Arch Biochem Biophys 243:1–7

    Article  CAS  PubMed  Google Scholar 

  • Shepherd GMG, Harris KM (1998) Three-dimensional structure and composition of CA3-CA1 axons in rat hippocampal slices: implications for presynaptic connectivity and compartmentalization. J Neurosci 18:8300–8310

    CAS  PubMed  Google Scholar 

  • Sherry DM, Wang MM, Bates J, Frishman LJ (2003) Expression of vesicular glutamate transporter 1 in the retina reveals temporal ordering in development of rod vs. cone and ON vs. OFF circuits. J Comp Neurol 465:480–498

    Article  CAS  PubMed  Google Scholar 

  • Shioi J, Ueda T (1990) Artificially imposed electrical potentials drive L-glutamate uptake into synaptic vesicles of bovine cerebral cortex. Biochem J 267:63–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shioi J, Naito S, Ueda T (1989) Glutamate uptake into synaptic vesicles of bovine cerebral cortex and electrochemical potential difference of proton across the membrane. Biochem J 258:499–504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith SJ (1992) Do astrocytes process neural information? Prog Brain Res 94:119–136

    Article  CAS  PubMed  Google Scholar 

  • Sonnewald U (2014) Glutamate synthesis has to be matched by its degradation—where do all the carbons go? J Neurochem 131:399–406

    Article  CAS  PubMed  Google Scholar 

  • Sonnewald U, Rae C (2010) Pyruvate carboxylation in different model systems studied by 13C MRS. Neurochem Res 35:1916–1921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stenovec M, Kreft M, Grilc S, Potokar M, Kreft ME, Pangrsic T, Zorec R (2007) Ca2+-dependent mobility of vesicles capturing anti-VGLUT1 antibodies. Exp Cell Res 313:3809–3818

    Article  CAS  PubMed  Google Scholar 

  • Storm-Mathisen J, Leknes AK, Bore AT, Vaaland JL, Edminson P, Haug E-M S, Ottersen OP (1983) First visualization of glutamate and GABA in neurons by immunocytochemistry. Nature 301:517–520

    Article  CAS  PubMed  Google Scholar 

  • Stornetta RL, Sevigny CP, Guyenet PG (2002) Vesicular glutamate transporter DNPI/VGLUT2 mRNA is present in C1 and several other groups of brainstem catecholaminergic neurons. J Comp Neurol 444:191–206

    Article  CAS  PubMed  Google Scholar 

  • Stornetta RL, Sevigny CP, Guyenet PG (2003) Inspiratory augmenting bulbospinal neurons express both glutamatergic and enkephalinergic phenotypes. J Comp Neurol 455:113–124

    Article  CAS  PubMed  Google Scholar 

  • Südhof TC (1990) The structure of the human synapsin I gene and protein. J Biol Chem 265:7849–7852

    PubMed  Google Scholar 

  • Südhof TC, Czernik AJ, Kao HT, Takei K, Johnston PA, Horiuchi A, Kanazir SD, Wagner MA, Perin MS, De Camilli P, Greengard P (1989) Synapsins: mosaics of shared and individual domains in a family of synaptic vesicle phosphoproteins. Science 245:1474–1480

    Article  PubMed  Google Scholar 

  • Tabb JS, Ueda T (1991) Phylogenetic studies on the synaptic vesicle glutamate transport system. J Neurosci 11:1822–1828

    CAS  PubMed  Google Scholar 

  • Tabb JS, Kish PE, Van Dyke R, Ueda T (1992) Glutamate transport into synaptic vesicles. Roles of membrane potential, pH gradient, and intravesicular pH. J Biol Chem 267:15412–15418

    CAS  PubMed  Google Scholar 

  • Takamori S, Rhee JS, Rosenmund C, Jahn R (2000) Identification of a vesicular glutamate transporter that defines a glutamatergic phenotype in neurons. Nature 407:189–194

    Article  CAS  PubMed  Google Scholar 

  • Takamori S, Rhee JS, Rosenmund C, Jahn R (2001) Identification of differentiation-associated brain-specific phosphate transporter as a second vesicular glutamate transporter (VGLUT2). J Neurosci 21:RC182

    CAS  PubMed  Google Scholar 

  • Takamori S, Malherbe P, Broger C, Jahn R (2002) Molecular cloning and functional characterization of human vesicular glutamate transporter 3. EMBO Rep 3:798–803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takamori S, Holt M, Stenius K, Lemke EA, Grønborg M, Riedel D, Urlaub H, Schenck S, Brügger B, Ringler P, Müller SA, Rammner B, Gräter F, Hub JS, De Groot BL, Mieskes G, Moriyama Y, Klingauf J, Grubmüller H, Heuser J, Wieland F, Jahn R (2006) Molecular Anatomy of a Trafficking Organelle. Cell 127:831–846

    Article  CAS  PubMed  Google Scholar 

  • Takeda K, Ueda T (2016) Effective mechanism for synthesis of neurotransmitter glutamate and its loading into synaptic vesicles. Neurochem Res. doi:10.1007/s11064-016-2037-3

    PubMed  Google Scholar 

  • Takeda K, Ishida A, Takahashi K, Ueda T (2012) Synaptic vesicles are capable of synthesizing the VGLUT substrate glutamate from α-ketoglutarate for vesicular loading. J Neurochem 121:184–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tamura Y, Ogita K, Ueda T (2014) A new VGLUT-specific potent inhibitor: pharmacophore of Brilliant Yellow. Neurochem Res 39:117–128

    Article  CAS  PubMed  Google Scholar 

  • Thompson CM, Davis E, Carrigan CN, Cox HD, Bridges RJ, Gerdes JM (2005) Inhibitors of the glutamate vesicular transporter (VGLUT). Curr Med Chem 12:2041–2056

    Article  CAS  PubMed  Google Scholar 

  • Tildon JT, Roeder LM, Stevenson JH (1985) Substrate oxidation by isolated rat brain mitochondria and synaptosomes. J Neurosci Res 14:207–215

    Article  CAS  PubMed  Google Scholar 

  • Todd AJ, Hughes DI, Polgár E, Nagy GG, Mackie M, Ottersen OP, Maxwell DJ (2003) The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal horn. Eur J Neurosci 17:13–27

    Article  CAS  PubMed  Google Scholar 

  • Todera R, Totterdell S, Wojcik S, Brose N, Elizalde N, Lasheras B, Rio J (2007) Enhanced anxiety, depressive-like behaviour and impaired recognition memory in mice with reduced expression of the vesicular glutamate transporter 1 (VGLUT1). Eur J Neurosci 25:281–290

    Article  Google Scholar 

  • Touret M, Parrot S, Denoroy L, Belin M-F, Didier-Bazes M (2007) Glutamatergic alterations in the cortex of genetic absence epilepsy rats. BMC Neurosci 8:69–76

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ueda T (1986) Glutamate transport in the synaptic vesicle. In: Roberts PJ, Storm-Mathisen J, Bradford H (eds) Excitatory amino acids. Macmillan, London, pp 173–195

    Chapter  Google Scholar 

  • Ueda T, Greengard P (1997) Adenosine 3′:5′-monophosphate-regulated phosphoprotein system of neuronal membranes. I. Solubilization, purification, and some properties of an endogenous phosphoprotein. J Biol Chem 252:5155–5163

    Google Scholar 

  • Ueda T, Ikemoto A (2007) Cytoplasmic glycolytic enzymes. Synaptic vesicle-associated glycolytic ATP-generating enzymes: coupling to neurotransmitter accumulation. In: Gibson G, Dienel G (eds) Handbook of neurochemistry and molecular neurobiology, 3rd edn, Brain energetics, cellular and molecular integration. Springer, Heidelberg, pp 241–259

    Chapter  Google Scholar 

  • Ueda T, Greengard P, Berzins K, Cohen RS, Blomberg F, Grab DJ, Siekevitz P (1979) Subcellular distribution in cerebral cortex of two proteins phosphorylated by a cAMP-dependent protein kinase. J Cell Biol 83:308–319

    Article  CAS  PubMed  Google Scholar 

  • Uehara S, Jung SK, Morimoto R, Arioka S, Miyaji T, Juge N, Hiasa M, Shimizu K, Ishimura A, Otsuka M, Yamamoto A, Maechler P, Moriyama Y (2006) Vesicular storage and secretion of L-glutamate from glucagon-like peptide 1-secreting clonal intestinal L cells. J Neurochem 96:550–560

    Article  CAS  PubMed  Google Scholar 

  • Uezato A, Meador-Woodruff JH, McCullumsmith RE (2009) Vesicular glutamate transporter mRNA expression in the medial temporal lobe in major depressive disorder, bipolar disorder, and schizophrenia. Bipolar Disord 11:711–725

    Article  CAS  PubMed  Google Scholar 

  • Van den Berg CJ, Garfinkel D (1971) A simulation study of brain compartments. Metabolism of glutamate and related substances in mouse brain. Biochem J 123:211–218

    Article  PubMed  Google Scholar 

  • Van der Hel WS, Verlinde SA, Meijer DH, de Wit M, Rensen MG, van Gassen KL, van Rijen PC, van Veelen CW, de Graan PN (2009) Hippocampal distribution of vesicular glutamate transporter 1 in patients with temporal lobe epilepsy. Epilepsia 50:1717–1728

    Article  PubMed  CAS  Google Scholar 

  • Varea E, Guirado R, Gilabert-Juan J, Martí U, Castillo-Gomez E, Blasco-Ibáñez JM, Crespo C, Nacher J (2012) Expression of PSA-NCAM and synaptic proteins in the amygdala of psychiatric disorder patients. J Psychiatr Res 46:189–197

    Article  PubMed  Google Scholar 

  • Varoqui H, Schafer MK-H, Zhu H, Weihe E, Erickson JD (2002) Identification of the differentiation-associated Na+/Pi transporter as a novel vesicular glutamate transporter expressed in a distinct set of glutamatergic synapses. J Neurosci 22:142–155

    CAS  PubMed  Google Scholar 

  • Verheijen FW, Verbeek E, Aula N, Beerens CE, Havelaar AC, Joosse M, Peltonen L, Aula P, Galjaard H, van der Spek PJ, Mancini GM (1999) A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases. Nat Genet 23:462–465

    Article  CAS  PubMed  Google Scholar 

  • Vossel KA, Beagle AJ, Rabinovici GD, Shu H, Lee SE, Naasan G, Hegde M, Cornes SB, Henry ML, Nelson AB, Seeley WW, Geschwind MD, Gorno-Tempini ML, Shih T, Kirsch HE, Garcia PA, Miller BL, Mucke L (2013) Seizures and epileptiform activity in the early stages of Alzheimer disease. JAMA Neurol 70:1158–1166

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang ZT, Yu G, Wang HS, Yi SP, Su RB, Gong ZH (2015) Changes in VGLUT2 expression and function in pain-related supraspinal regions correlate with the pathogenesis of neuropathic pain in a mouse spared nerve injury model. Brain Res 1624:515–524

    Article  CAS  PubMed  Google Scholar 

  • Watkins JC, Evans RH (1981) Excitatory amino acid transmitters. Annu. Rev Pharmacol Toxicol 21:165–204

    Article  CAS  Google Scholar 

  • Westergaard N, Sonnewald U, Schousboe A (1994) Release of α-ketoglutarate, malate and succinate from cultured astrocytes: possible role in amino acid neurotransmitter homeostasis. Neurosci Lett 176:105–109

    Article  CAS  PubMed  Google Scholar 

  • Weston MC, Stornetta RL, Guyenet PG (2004) Glutamatergic neuronal projections from the marginal layer of the rostral ventral medulla to the respiratory centers in rats. J Comp Neurol 473:73–85

    Article  PubMed  Google Scholar 

  • Weston MC, Nehring RB, Wojcik SM, Rosenmund C (2011) Interplay between VGLUT isoforms and endophilin A1 regulates neurotransmitter release and short-term plasticity. Neuron 69:1147–1159

    Article  CAS  PubMed  Google Scholar 

  • Wilson NR, Kang J, Hueske EV, Leung T, Varoqui H, Murnick JG, Erickson JD, Liu G (2005) Presynaptic regulation of quantal size by the vesicular glutamate transporter VGLUT1. J Neurosci 25:6221–6234

    Article  CAS  PubMed  Google Scholar 

  • Winter HC, Ueda T (1993) Glutamate uptake system in the presynaptic vesicle: glutamic acid analogs as inhibitors and alternative substrates. Neurochem Res 18:79–85

    Article  CAS  PubMed  Google Scholar 

  • Winter HC, Ueda T (2008) The glutamate uptake system in presynaptic vesicles: further characterization of structural requirements for inhibitors and substrates. Neurochem Res 33:223–231

    Article  CAS  PubMed  Google Scholar 

  • Wojcik SM, Rhee CJS, Herzog E, Sigler A, Jahn R, Takamori S, Brose N, Rosenmund C (2004) An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size. Proc Natl Acad Sci U S A 101:7158–7163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wolosker H, de Souza DO, de Meis L (1996) Regulation of glutamate transport into synaptic vesicles by chloride and proton gradient. J Biol Chem 271:11726–11731

    Article  CAS  PubMed  Google Scholar 

  • Wu SX, Koshimizu Y, Feng YP, Okamoto K, Fujiyama F, Hioki H, Li YQ, Kaneko T, Mizuno N (2004) Vesicular glutamate transporter immunoreactivity in the central and peripheral endings of muscle-spindle afferents. Brain Res 1011:247–251

    Article  CAS  PubMed  Google Scholar 

  • Yu AC, Drejer J, Hertz L, Schousboe A (1983) Pyruvate carboxylase activity in primary cultures of astrocytes and neurons. J Neurochem 41:1484–1487

    Article  CAS  PubMed  Google Scholar 

  • Zala D, Hinckelmann MV, Yu H, Lyra da Cunha MM, Liot G, Cordelières FP, Marco S, Saudou F (2013) Vesicular glycolysis provides on-board energy for fast axonal transport. Cell 152:479–491

    Article  CAS  PubMed  Google Scholar 

  • Zerari-Mailly F, Braud A, Davido N, Touré B, Azérad J, Boucher Y (2012) Glutamate control of pulpal blood flow in the incisor dental pulp of the rat. Eur J Oral Sci 120:402–407

    Article  CAS  PubMed  Google Scholar 

  • Zhang Q, Pangrsic T, Kreft M, Krzan M, Li N, Sul JY, Halassa M, Van Bockstaele E, Zorec R, Haydon PG (2004) Fusion-related release of glutamate from astrocytes. J Biol Chem 279:12724–12733

    Article  CAS  PubMed  Google Scholar 

  • Zhou J, Nannapaneni N, Shore S (2007) Vesicular glutamate transporters 1 and 2 are differentially associated with auditory nerve and spinal trigeminal inputs to the cochlear nucleus. J Comp Neurol 500:777–787

    Article  CAS  PubMed  Google Scholar 

  • Zieminska E, Hilgier W, Waagepetersen HS, Hertz L, Sonnewald U, Schousboe A, Albrecht J (2004) Analysis of glutamine accumulation in rat brain mitochondria in the presence of a glutamine uptake inhibitor, histidine, reveals glutamine pools with a distinct access to deamidation. Neurochem Res 29:2121–2123

    Article  CAS  PubMed  Google Scholar 

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Acknowledgement

I thank Dr. Minor J Coon, Dr. Stephen K. Fisher, Dr. John T. Hackett, Dr. Francis S. Lee, and Yasuko Ueda for critical reading and comments, and the computer consultant Douglass Smith and Yasuko Ueda for making model figure illustrations.

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  1. Molecular and Behavioral Neuroscience Institute, The University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA

    Tetsufumi Ueda

  2. Department of Pharmacology, University of Michigan Medical School, 2301 MSRB III, 1150 W. Medical Center Dr., Ann Arbor, MI, 48109-5632, USA

    Tetsufumi Ueda

  3. Department of Psychiatry, Medical School, The University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA

    Tetsufumi Ueda

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  1. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Arne Schousboe

  2. Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    Ursula Sonnewald

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Ueda, T. (2016). Vesicular Glutamate Uptake. In: Schousboe, A., Sonnewald, U. (eds) The Glutamate/GABA-Glutamine Cycle. Advances in Neurobiology, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-319-45096-4_7

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