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Distribution of the glutamate transporters GLT-1 (SLC1A2) and GLAST (SLC1A3) in peripheral organs

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Abstract

The glutamate transporters GLT-1 and GLAST are widely expressed in astrocytes in the brain where they fulfill important functions during glutamatergic neurotransmission. The present study examines their distribution in peripheral organs using in situ hybridization (ISH) and immunocytochemistry. GLAST was found to be more widely distributed than GLT-1. GLAST was expressed primarily in epithelial cells, cells of the macrophage-lineage, lymphocytes, fat cells, interstitial cells, and salivary gland acini. GLT-1 was primarily expressed in glandular tissue, including mammary gland, lacrimal gland, and ducts and acini in salivary glands, but also by perivenous hepatocytes and follicular dendritic cells in spleen and lymph nodes. The findings demonstrate that, although expressed by the same cells in the brain, these two glutamate transporters have different distribution patterns in peripheral tissues and that they fulfill glutamate transport functions apart from glutamatergic neurotransmission in these areas.

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Reference

  • Arriza JL, Fairman WA, Wadiche JI, Murdoch GH, Kavanaugh MP, Amara SG (1994) Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J Neurosci 14:5559–5569

    PubMed  CAS  Google Scholar 

  • Berger UV, Hediger MA (1998) Comparative analysis of glutamate transporter expression in rat brain using differential double in situ hybridization. Anat Embryol (Berl) 198:13–30

    Article  CAS  Google Scholar 

  • Berger UV, Hediger MA (2000) Distribution of the glutamate transporters GLAST and GLT-1 in rat circumventricular organs, meninges, and dorsal root ganglia. J Comp Neurol 421:385–399

    Article  PubMed  CAS  Google Scholar 

  • Berger UV, Hediger MA (2001) Differential distribution of the glutamate transporters GLT-1 and GLAST in tanycytes of the third ventricle. J Comp Neurol 433:101–114

    Article  PubMed  CAS  Google Scholar 

  • Cadoret A, Ovejero C, Terris B, Souil E, Levy L, Lamers WH, Kitajewski J, Kahn A, Perret C (2002) New targets of beta-catenin signaling in the liver are involved in the glutamine metabolism. Oncogene 21:8293–8301

    Article  PubMed  CAS  Google Scholar 

  • Chen W, Mahadomrongkul V, Berger UV, Bassan M, DeSilva T, Tanaka K, Irwin N, Aoki C, Rosenberg PA (2004) The glutamate transporter GLT1a is expressed in excitatory axon terminals of mature hippocampal neurons. J Neurosci 24:1136–1148

    Article  PubMed  CAS  Google Scholar 

  • Chretien F, Vallat-Decouvelaere AV, Bossuet C, Rimaniol AC, Le Grand R, Le Pavec G, Creminon C, Dormont D, Gray F, Gras G (2002) Expression of excitatory amino acid transporter-2 (EAAT-2) and glutamine synthetase (GS) in brain macrophages and microglia of SIVmac251-infected macaques. Neuropathol Appl Neurobiol 28:410–417

    Article  PubMed  CAS  Google Scholar 

  • Costello LC, Franklin RB (2002) Testosterone and prolactin regulation of metabolic genes and citrate metabolism of prostate epithelial cells. Horm Metabol Res 34:417–424

    Article  CAS  Google Scholar 

  • Franklin RB, Zou J, Yu Z, Costello LC (2006) EAAC1 is expressed in rat and human prostate epithelial cells; functions as a high-affinity L-aspartate transporter; and is regulated by prolactin and testosterone. BMC Biochem 7:10

    Article  PubMed  CAS  Google Scholar 

  • Furness DN, Hulme JA, Lawton DM, Hackney CM (2002) Distribution of the glutamate/aspartate transporter GLAST in relation to the afferent synapses of outer hair cells in the guinea pig cochlea. J Assoc Res Otolaryngol 3:234–247

    Article  PubMed  Google Scholar 

  • Furness DN, Lehre KP (1997) Immunocytochemical localization of a high-affinity glutamate-aspartate transporter, GLAST, in the rat and guinea-pig cochlea. Eur J Neurosci 9:1961–1969

    Article  PubMed  CAS  Google Scholar 

  • Haugeto O, Ullensvang K, Levy LM, Chaudhry FA, Honore T, Nielsen M, Lehre KP, Danbolt NC (1996) Brain glutamate transporter proteins form homomultimers. J Biol Chem 271:27715–27722

    Article  PubMed  CAS  Google Scholar 

  • Hediger MA (1999) Glutamate transporters in kidney and brain. Am J Physiol 277:F487–F492

    PubMed  CAS  Google Scholar 

  • Hediger MA, Welbourne TC (1999) Introduction: glutamate transport, metabolism, and physiological responses. Am J Physiol 277:F477–F480

    PubMed  CAS  Google Scholar 

  • Howell JA, Matthews AD, Swanson KC, Harmon DL, Matthews JC (2001) Molecular identification of high-affinity glutamate transporters in sheep and cattle forestomach, intestine, liver, kidney, and pancreas. J Anim Sci 79:1329–1336

    PubMed  CAS  Google Scholar 

  • Howell JA, Matthews AD, Welbourne TC, Matthews JC (2003) Content of ileal EAAC1 and hepatic GLT-1 high-affinity glutamate transporters is increased in growing vs. nongrowing lambs, paralleling increased tissue D- and L-glutamate, plasma glutamine, and alanine concentrations. J Anim Sci 81:1030–1039

    CAS  Google Scholar 

  • Kanai Y, Hediger MA (2004) The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects. Pflugers Arch 447:469–479

    Article  PubMed  CAS  Google Scholar 

  • Kawakami H, Tanaka K, Nakayama T, Inoue K, Nakamura S (1994) Cloning and expression of a human glutamate transporter. Biochem Biophys Res Commun 199:171–176

    Article  PubMed  CAS  Google Scholar 

  • Kirschner MA, Copeland NG, Gilbert DJ, Jenkins NA, Amara SG (1994) Mouse excitatory amino acid transporter EAAT2: isolation, characterization, and proximity to neuroexcitability loci on mouse chromosome 2. Genomics 24:218–224

    Article  PubMed  CAS  Google Scholar 

  • Kondo K, Hashimoto H, Kitanaka J, Sawada M, Suzumura A, Marunouchi T, Baba A (1995) Expression of glutamate transporters in cultured glial cells. Neurosci Lett 188:140–142

    Article  PubMed  CAS  Google Scholar 

  • Kugler P, Schmitt A (2003) Complementary neuronal and glial expression of two high-affinity glutamate transporter GLT1/EAAT2 forms in rat cerebral cortex. Histochem Cell Biol 119:425–435

    Article  PubMed  CAS  Google Scholar 

  • Lao L, Franklin RB, Costello LC (1993) High-affinity L-aspartate transporter in prostate epithelial cells that is regulated by testosterone. Prostate 22:53–63

    Article  PubMed  CAS  Google Scholar 

  • Lawton DM, Furness DN, Lindemann B, Hackney CM (2000) Localization of the glutamate-aspartate transporter, GLAST, in rat taste buds. Eur J Neurosci 12:3163–3171

    Article  PubMed  CAS  Google Scholar 

  • Lehre KP, Levy LM, Ottersen OP, Storm-Mathisen J, Danbolt NC (1995) Differential expression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations. J Neurosci 15:1835–1853

    PubMed  CAS  Google Scholar 

  • Li HS, Niedzielski AS, Beisel KW, Hiel H, Wenthold RJ, Morley BJ (1994) Identification of a glutamate/aspartate transporter in the rat cochlea. Hear Res 78:235–242

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Lopez I, Garcia C, Barber T, Vina JR, Miralles VJ (1998) The L-glutamate transporters GLAST (EAAT1) and GLT-1 (EAAT2): expression and regulation in rat lactating mammary gland. Mol Membr Biol 15:237–242

    Article  PubMed  CAS  Google Scholar 

  • Mason DJ (2004) The role of glutamate transporters in bone cell signalling. J Musculoskelet Neuronal Interact 4:128–131

    PubMed  CAS  Google Scholar 

  • Mason DJ, Suva LJ, Genever PG, Patton AJ, Steuckle S, Hillam RA, Skerry TM (1997) Mechanically regulated expression of a neural glutamate transporter in bone: a role for excitatory amino acids as osteotropic agents? Bone 20:199–205

    Article  PubMed  CAS  Google Scholar 

  • Matsuzaki T, Suzuki T, Koyama H, Tanaka S, Takata K (1999) Water channel protein AQP3 is present in epithelia exposed to the environment of possible water loss. J Histochem Cytochem 47:1275–1286

    PubMed  CAS  Google Scholar 

  • Matthews JC, Beveridge MJ, Malandro MS, Rothstein JD, Campbell-Thompson M, Verlander JW, Kilberg MS, Novak DA (1998) Activity and protein localization of multiple glutamate transporters in gestation day 14 vs. day 20 rat placenta. Am J Physiol 274:C603–C614

    PubMed  CAS  Google Scholar 

  • Mirels L, Kopec L, Yagil C, Dickinson DP, Dziejman M, Tabak LA (1990) Expression of glutamine/glutamic acid-rich proteins in rat submandibular glands. Arch Oral Biol 35:1–5

    Article  PubMed  CAS  Google Scholar 

  • Nauntofte B (1992) Regulation of electrolyte and fluid secretion in salivary acinar cells. Am J Physiol 263:G823–G837

    PubMed  CAS  Google Scholar 

  • Noda M, Nakanishi H, Akaike N (1999) Glutamate release from microglia via glutamate transporter is enhanced by amyloid-beta peptide. Neuroscience 92:1465–1474

    Article  PubMed  CAS  Google Scholar 

  • Redecker P, Kreutz MR, Bockmann J, Gundelfinger ED, Boeckers TM (2003) Brain synaptic junctional proteins at the acrosome of rat testicular germ cells. J Histochem Cytochem 51:809–819

    PubMed  CAS  Google Scholar 

  • Redecker P, Pabst H (2000) Immunohistochemical study of the glutamate transporter proteins GLT-1 and GLAST in rat and gerbil pineal gland. J Pineal Res 28:179–184

    Article  PubMed  CAS  Google Scholar 

  • Rimaniol AC, Haik S, Martin M, Le Grand R, Boussin FD, Dereuddre-Bosquet N, Gras G, Dormont D (2000) Na+-dependent high-affinity glutamate transport in macrophages. J Immunol 164:5430–5438

    PubMed  CAS  Google Scholar 

  • Rimaniol AC, Mialocq P, Clayette P, Dormont D, Gras G (2001) Role of glutamate transporters in the regulation of glutathione levels in human macrophages. Am J Physiol Cell Physiol 281:C1964–C1970

    PubMed  CAS  Google Scholar 

  • Shashidharan P, Wittenberg I, Plaitakis A (1994) Molecular cloning of human brain glutamate/aspartate transporter II. Biochim Biophys Acta 1191:393–396

    Article  PubMed  CAS  Google Scholar 

  • Shayakul C, Kanai Y, Lee WS, Brown D, Rothstein JD, Hediger MA (1997) Localization of the high-affinity glutamate transporter EAAC1 in rat kidney. Am J Physiol 273:F1023–F1029

    PubMed  CAS  Google Scholar 

  • Tanaka K (1993) Expression cloning of a rat glutamate transporter. Neurosci Res 16:149–153

    Article  PubMed  CAS  Google Scholar 

  • Utsunomiya-Tate N, Endou H, Kanai Y (1997) Tissue specific variants of glutamate transporter GLT-1. FEBS Lett 416:312–316

    Article  PubMed  CAS  Google Scholar 

  • van Landeghem FK, Stover JF, Bechmann I, Bruck W, Unterberg A, Buhrer C, von Deimling A (2001) Early expression of glutamate transporter proteins in ramified microglia after controlled cortical impact injury in the rat. Glia 35:167–179

    Article  PubMed  Google Scholar 

  • Wagenfeld A, Yeung CH, Lehnert W, Nieschlag E, Cooper TG (2002) Lack of glutamate transporter EAAC1 in the epididymis of infertile c-ros receptor tyrosine-kinase deficient mice. J Androl 23:772–782

    PubMed  CAS  Google Scholar 

  • Welbourne T, Routh R, Yudkoff M, Nissim I (2001) The glutamine/glutamate couplet and cellular function. News Physiol Sci16:157–160

    Google Scholar 

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Acknowledgment

We thank Niels Christian Danbolt from the University of Oslo, Norway for providing the antibodies against GLT-1 and GLAST.

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Correspondence to Matthias A. Hediger.

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Berger, U.V., Hediger, M.A. Distribution of the glutamate transporters GLT-1 (SLC1A2) and GLAST (SLC1A3) in peripheral organs. Anat Embryol 211, 595–606 (2006). https://doi.org/10.1007/s00429-006-0109-x

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  • DOI: https://doi.org/10.1007/s00429-006-0109-x

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