Skip to main content

Advertisement

SpringerLink
Log in

Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family

  • The ABC of Solute carriers
  • Guest Editor: Matthias A. Hediger
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

The sodium-coupled neutral amino acid transporters (SNAT) of the SLC38 gene family resemble the classically-described System A and System N transport activities in terms of their functional properties and patterns of regulation. Transport of small, aliphatic amino acids by System A subtypes (SNAT1, SNAT2, and SNAT4) is rheogenic and pH sensitive. The System N subtypes SNAT3 and SNAT5 also countertransport H+, which may be key to their operation in reverse, and have narrower substrate profiles than do the System A subtypes. Glutamine emerges as a favored substrate throughout the family, except for SNAT4. The SLC38 transporters undoubtedly play many physiological roles including the transfer of glutamine from astrocyte to neuron in the CNS, ammonia detoxification and gluconeogenesis in the liver, and the renal response to acidosis. Probing their regulation has revealed additional roles, and recent work has considered SLC38 transporters as therapeutic targets in neoplasia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3A, B.

Similar content being viewed by others

Notes

  1. We propose here that the transporters of the SLC38 gene family be renamed SNAT1–6, numbered in line with the corresponding gene symbols (see Table 1). We suggest that SNAT should stand for "Sodium-coupled Neutral Amino acid Transporter" (and also recall the classic transport activities, i.e., "System N/A Transporter"). An overwhelming majority of the investigators consulted support the revised nomenclature. Those polled included S. Bröer, F.A. Chaudhry, F. Conti, R.H. Edwards, V. Ganapathy, M.A. Hediger, H.S. Hundal, J.X. Jiang, M.S. Kilberg, M. Matteoli, J.C. Matthews, H. Varoqui, and E. Weihe.

References

  1. Ahmed A, Taylor PM, Rennie MJ (1990) Characteristics of glutamine transport in sarcolemmal vesicles from rat skeletal muscle. Am J Physiol 259:E284–E291

    PubMed  Google Scholar 

  2. Albers A, Bröer A, Wagner CA, Setiawan I, Lang PA, Kranz EU, Lang F, Bröer S (2001) Na+ transport by the neural glutamine transporter ATA1. Pflugers Arch 443:92–101

    Article  CAS  PubMed  Google Scholar 

  3. Alfieri RR, Petronini P-G, Bonelli MA, Caccamo AE, Cavazzoni A, Borghetti AF, Wheeler KP (2001) Osmotic regulation of ATA2 mRNA expression and amino acid transport System A activity. Biochem Biophys Res Commun 283:174–178

    CAS  PubMed  Google Scholar 

  4. Armano S, Coco S, Bacci A, Pravettoni E, Schenk U, Verderio C, Varoqui H, Erickson JD, Matteoli M (2002) Localization and functional relevance of system A neutral amino acid transporters in cultured hippocampal neurons. J Biol Chem 277:10467–10473

    Article  PubMed  Google Scholar 

  5. Bain PJ, LeBlanc-Chaffin R, Chen H, Palii SS, Leach KM, Kilberg MS (2002) The mechanism for transcriptional activation of the human ATA2 transporter gene by amino acid deprivation is different than that for asparagine synthetase. J Nutr 132:3023–3029

    PubMed  Google Scholar 

  6. Berk JL, Hatch CA, Goldstein RH (2000) Hypoxia inhibits amino acid uptake in human lung fibroblasts. J Appl Physiol 89:1425–1431

    PubMed  Google Scholar 

  7. Bhat HK, Vadgama JV (2002) Role of estrogen receptor in the regulation of estrogen induced amino acid transport of System A in breast cancer and other receptor positive tumor cells. Int J Mol Med 9:271–279

    PubMed  Google Scholar 

  8. Boulland J-L, Osen KK, Levy LM, Danbolt NC, Edwards RH, Storm-Mathisen J, Chaudhry FA (2002) Cell-specific expression of the glutamine transporter SN1 suggests differences in dependence on the glutamine cycle. Eur J Neurosci 15:1615–1631

    Article  PubMed  Google Scholar 

  9. Boulland J-L, Rafiki A, Levy LM, Storm-Mathisen J, Chaudhry FA (2003) Highly differential expression of SN1, a bidirectional glutamine transporter, in astroglia and endothelium in the developing rat brain. Glia 41:260–275

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  11. Bröer A, Brookes N, Ganapathy V, Dimmer KS, Wagner CA, Lang F, Bröer S (1999) The astroglial ASCT2 amino acid transporter as a mediator of glutamine efflux. J Neurochem 73:2184–2194

    CAS  PubMed  Google Scholar 

  12. Bröer A, Albers A, Setiawan I, Edwards RH, Chaudhry FA, Lang F, Wagner CA, Bröer S (2002) Regulation of the glutamine transporter SN1 by extracellular pH and intracellular sodium ions. J Physiol (Lond) 539:3–14

    Google Scholar 

  13. Bröer S, Brookes N (2001) Transfer of glutamine between astrocytes and neurons. J Neurochem 77:705–719

    CAS  PubMed  Google Scholar 

  14. Brookes N, Turner RJ (1993) Extracellular potassium regulates the glutamine content of astrocytes: mediation by intracellular pH. Neurosci Lett 160:73–76

    PubMed  Google Scholar 

  15. Chaudhry FA, Reimer RJ, Krizaj D, Barber D, Storm-Mathisen J, Copenhagen DR, Edwards RH (1999) Molecular analysis of system N suggests novel physiological roles in nitrogen metabolism and synaptic transmission. Cell 99:769–780

    CAS  PubMed  Google Scholar 

  16. Chaudhry FA, Krizaj D, Larsson P, Reimer RJ, Wreden C, Storm-Mathisen J, Copenhagen D, Kavanaugh M, Edwards RH (2001) Coupled and uncoupled proton movement by amino acid transport system N. EMBO J 20:7041–7051

    CAS  PubMed  Google Scholar 

  17. Chaudhry FA, Schmitz D, Reimer RJ, Larsson P, Gray AT, Nicoll R, Kavanaugh M, Edwards RH (2002) Glutamine uptake by neurons: interaction of protons with System A transporters. J Neurosci 22:62–72

    PubMed  Google Scholar 

  18. Choi YH, Chang N, Fletcher PJ, Anderson GH (2000) Dietary protein content affects the profiles of extracellular amino acids in the medial preoptic area of freely moving rats. Life Sci 66:1105–1118

    Article  PubMed  Google Scholar 

  19. Christensen HN (1948) Distribution of amino acids between cellular and extracellular fluids. Relation to growth. Bull N Engl Med Ctr 10:108–111

    Google Scholar 

  20. Christensen HN (1982) Interorgan amino acid nutrition. Physiol Rev 62:1193–1233

    PubMed  Google Scholar 

  21. Christensen HN (1990) Role of amino acid transport and countertransport in nutrition and metabolism. Physiol Rev 70:43–77

    CAS  PubMed  Google Scholar 

  22. Christensen HN, Handlogten ME (1977) Na+/Li+ selectivity in transport System A: effects of substrate structure. J Membr Biol 37:193–211

    PubMed  Google Scholar 

  23. Christensen HN, Oxender DL, Liang M, Vatz KA (1965) The use of N-methylation to direct the route of mediated transport of amino acids. J Biol Chem 240:3609–3616

    CAS  PubMed  Google Scholar 

  24. Conti F, Minelli A (1994) Glutamate immunoreactivity in rat cerebral cortex is reversibly abolished by 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of phosphate-activated glutaminase. J Histochem Cytochem 42:717–726

    PubMed  Google Scholar 

  25. Ensenat D, Hassan S, Reyna SV, Schafer AI, Durante W (2001) Transforming growth factor-β 1 stimulates vascular smooth muscle cell L-proline transport by inducing system A amino acid transporter 2 (SAT2) gene expression. Biochem J 360:507–512

    Article  PubMed  Google Scholar 

  26. Erecińska M, Nelson D, Nissim I, Daikhin Y, Yudkoff M (1994) Cerebral alanine transport and alanine aminotransferase reaction: alanine as a source of neuronal glutamate. J Neurochem 62:1953–1964

    PubMed  Google Scholar 

  27. Fei YJ, Sugawara M, Nakanishi T, Huang W, Wang H, Prasad PD, Leibach FH, Ganapathy V (2000) Primary structure, genomic organization, and functional and electrogenic characteristics of human System N1, a Na+- and H+-coupled glutamine transporter. J Biol Chem 275:23707–23717

    Article  PubMed  Google Scholar 

  28. Franchi-Gazzola R, Sala R, Bussolati O, Visigalli R, Dall'Asta V, Ganapathy V, Gazzola GC (2001) The adaptive regulation of amino acid transport system A is associated to changes in ATA2 expression. FEBS Lett 490:11–14

    Article  PubMed  Google Scholar 

  29. Gu S, Roderick HL, Camacho P, Jiang JX (2000) Identification and characterization of an amino acid transporter expressed differentially in liver. Proc Natl Acad Sci USA 97:3230–3235

    Article  PubMed  Google Scholar 

  30. Gu S, Adan-Rice D, Leach RJ, Jiang JX (2001) A novel human amino acid transporter, hNAT3: cDNA cloning, chromosomal mapping, genomic structure, expression, and functional characterization. Genomics 74:262–272

    Article  PubMed  Google Scholar 

  31. Gu S, Roderick HL, Camacho P, Jiang JX (2001) Characterization of an N-system amino acid transporter expressed in retina and its involvement in glutamine transport. J Biol Chem 276:24137–24144

    CAS  PubMed  Google Scholar 

  32. Gu S, Langlais P, Liu F, Jiang JX (2003) Mouse system-N amino acid transporter, mNAT3, expressed in hepatocytes and regulated by insulin-activated and phosphoinositide 3-kinase-dependent signalling. Biochem J 371:721–731

    Article  PubMed  Google Scholar 

  33. Gumà A, Testar X, Palacín M, Zorzano A (1988) Insulin-stimulated α-(methyl)aminoisobutyric acid uptake in skeletal muscle. Biochem J 253:625–629

    PubMed  Google Scholar 

  34. Hamberger AC, Chiang GH, Nylen 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  PubMed  Google Scholar 

  35. Hatanaka T, Huang W, Wang H, Sugawara M, Prasad PD, Leibach FH, Ganapathy V (2000) Primary structure, functional characteristics and tissue expression pattern of human ATA2, a subtype of amino acid transport system A. Biochim Biophys Acta 1467:1–6

    Article  PubMed  Google Scholar 

  36. Hatanaka T, Huang W, Martindale RG, Ganapathy V (2001) Differential influence of cAMP on the expression of the three subtypes (ATA1, ATA2, and ATA3) of the amino acid transport system A. FEBS Lett 505:317–320

    Article  PubMed  Google Scholar 

  37. Hatanaka T, Huang W, Ling R, Prasad PD, Sugawara M, Leibach FH, Ganapathy V (2001) Evidence for the transport of neutral as well as cationic amino acids by ATA3, a novel and liver-specific subtype of amino acid transport system A. Biochim Biophys Acta 1510:10–17

    Article  PubMed  Google Scholar 

  38. Häussinger D (1990) Nitrogen metabolism in liver: structural and functional organization and physiological relevance. Biochem J 267:281–290

    PubMed  Google Scholar 

  39. Häussinger D, Lang F, Kilberg MS (1992) Amino acid transport, cell volume and regulation of cell growth. In: Kilberg MS, Häussinger D (eds) Mammalian amino acid transport: mechanisms and control. Plenum Press, New York, pp 113–130

  40. Häussinger D, Schliess F, Kircheis G (2002) Pathogenesis of hepatic encephalopathy. J Gastroenterol Hepatol 17 (Suppl 3):S256–S259

    Article  PubMed  Google Scholar 

  41. Heckel T, Bröer A, Weisinger H, Lang F, Bröer S (2003) Asymmetry of glutamine transporters in cultured neural cells. Neurochem Int 43:289–298

    Article  PubMed  Google Scholar 

  42. Holman GD, Kasuga M (1997) From receptor to transporter: insulin signalling to glucose transport. Diabetogia 40:991–1003

    Article  Google Scholar 

  43. Hundal HS, Rennie MJ, Watt PW (1987) Characteristics of L-glutamine transport in perfused rat skeletal muscle. J Physiol (Lond) 393:283–305

    Google Scholar 

  44. Hyde R, Christie GR, Litherland GJ, Hajduch E, Taylor PM, Hundal HS (2001) Subcellular localization and adaptive up-regulation of the System A (SAT2) amino acid transporter in skeletal-muscle cells and adipocytes. Biochem J 355:563–568

    CAS  PubMed  Google Scholar 

  45. Hyde R, Peyrollier K, Hundal HS (2002) Insulin promotes the cell surface recruitment of the SAT2/ATA2 System A amino acid transporter from an endosomal compartment in skeletal muscles cells. J Biol Chem 277:13628–13634

    Article  PubMed  Google Scholar 

  46. Jacob R, Rosenthal N, Barrett EJ (1986) Characterization of glutamine transport by liver plasma membrane vesicles. Am J Physiol 251:E509–E514

    PubMed  Google Scholar 

  47. Kanai Y, Trotti D, Berger UV, Hediger MA (2002) The high-affinity glutamate and neutral amino-acid transporter family. In: Reith MEA (ed) Neurotransmitter transporters: structure, function and regulation. Humana Press, Totowa, pp 255–311

  48. Karinch AM, Lin C-M, Wolfgang CL, Pan M, Souba WW (2002) Regulation of expression of the SN1 transporter during renal adaptation to chronic metabolic acidosis in rats. Am J Physiol 283:F1011–F1019

    Google Scholar 

  49. Karlsen TV, Serck-Hanssen G (2002) Acute stimulation by IGF-I of amino acid transport system A in chromaffin cells depends on PI3 kinase activation and the electrochemical gradient of Na+. Ann NY Acad Sci 971:573–575

    PubMed  Google Scholar 

  50. Kilberg MS, Häussinger D (1992) Amino acid transport in liver. In: Kilberg MS, Häussinger D (eds) Mammalian amino acid transport: mechanisms and control. Plenum Press, New York, pp 133–148

  51. Kilberg MS, Handlogten ME, Christensen HN (1980) Characteristics of an amino acid transport system in rat liver for glutamine, asparagine, histidine, and closely related analogs. J Biol Chem 255:4011–4019

    CAS  PubMed  Google Scholar 

  52. Kilberg MS, Han HP, Barber EF, Chiles TC (1985) Adaptive regulation of neutral amino acid transport System A in rat H4 hepatoma cells. J Cell Physiol 122:290–298

    PubMed  Google Scholar 

  53. Laake JH, Slyngstad TA, Haug FM, Ottersen OP (1995) Glutamine from glial cells is essential for the maintenance of the nerve terminal pool of glutamate: immunogold evidence from hippocampal slice cultures. J Neurochem 65:871–881

    CAS  PubMed  Google Scholar 

  54. Ling R, Bridges CC, Sugawara M, Fujita T, Leibach FH, Prasad PD, Ganapathy V (2001) Involvement of transporter recruitment as well as gene expression in the substrate-induced adaptive regulation of amino acid transport system A. Biochim Biophys Acta 1512:15–21

    CAS  PubMed  Google Scholar 

  55. Low SY, Taylor PM, Ahmed A, Pogson CI, Rennie MJ (1991) Substrate-specificity of glutamine transporters in membrane vesicles from rat liver and skeletal muscle investigated using amino acid analogues. Biochem J 278:105–111

    CAS  PubMed  Google Scholar 

  56. Lund P (1980) Glutamine metabolism in the rat. FEBS Lett 117 (Suppl):K86–K92

    Article  PubMed  Google Scholar 

  57. Mackenzie B, Ahmed A, Rennie MJ (1992) Muscle amino acid metabolism and transport. In: Kilberg MS, Häussinger D (eds) Mammalian amino acid transport: mechanisms and control. Plenum Press, New York, pp 195–231

  58. Mackenzie B, Schäfer MKH, Erickson JD, Hediger MA, Weihe E, Varoqui H (2003) Functional properties and cellular distribution of the System A glutamine transporter SNAT1 support specialized roles in central neurons. J Biol Chem 278:23720–23730

    Article  Google Scholar 

  59. Mackenzie B, Yao D, Erickson JD, Hediger MA, Varoqui H (2003) Functional properties of the neuronal System A glutamine transporter (SAT1) and identification of a critical histidyl residue (abstract). FASEB J 17:A906

    Google Scholar 

  60. Mahendran D, Donnai P, Glazier JD, D'Souza SW, Boyd RDH, Sibley CP (1993) Amino acid (system A) transporter activity in microvillous membrane vesicles from the placentas of appropriate and small for gestational age babies. Pediatr Res 34:661–665

    PubMed  Google Scholar 

  61. Martarello L, McConathy J, Camp VM, Malveaux EJ, Simpson NE, Simpson CP, Olson JJ, Bowers GD, Goodman MM (2002) Synthesis of syn- and anti-1-amino-3-[18F]fluoromethyl-cyclobutane-1-carboxylic acid (FMACBC), potential PET ligands for tumor detection. J Med Chem 45:2250–2259

    Article  PubMed  Google Scholar 

  62. McConathy J, Martarello L, Malveaux EJ, Camp VM, Simpson NE, Simpson CP, Bowers GD, Olson JJ, Goodman MM (2002) Radiolabeled amino acids for tumor imaging with PET: radiosynthesis and biological evaluation of 2-amino-3-[18F]fluoro-2-methylpropanoic acid and 3-[18F]fluoro-2-methyl-2-(methylamino)propanoic acid. J Med Chem 45:2240–2249

    Article  PubMed  Google Scholar 

  63. McGivan JD, Pastor-Anglada M (1994) Regulatory and molecular aspects of mammalian amino acid transport. Biochem J 299:321–334

    CAS  PubMed  Google Scholar 

  64. McIntire SL, Reimer RJ, Schuske K, Edwards RH, Jorgensen EM (1997) Identification and characterization of the vesicular GABA transporter. Nature 389:870–876

    Article  CAS  PubMed  Google Scholar 

  65. Miyakawa H, Woo SK, Dahl SC, Handler JS, Kwon HM (1999) Tonicity-responsive enhancer binding protein, a rel-like protein that stimulates transcription in response to hypertonicity. Proc Natl Acad Sci USA 96:2538–2542

    CAS  PubMed  Google Scholar 

  66. Nagaraja TN, Brookes N (1996) Glutamine transport in mouse cerebral astrocytes. J Neurochem 66:1665–1674

    PubMed  Google Scholar 

  67. Nahm O, Woo SK, Handler JS, Kwon HM (2002) Involvement of multiple kinase pathways in stimulation of gene transcription by hypertonicity. Am J Physiol 282:C49–C58

    CAS  Google Scholar 

  68. Nakanishi T, Kekuda R, Fei YJ, Hatanaka T, Sugawara M, Martindale RG, Leibach FH, Prasad PD, Ganapathy V (2001) Cloning and functional characterization of a new subtype of the amino acid transport system N. Am J Physiol 281:C1757–C1768

    CAS  Google Scholar 

  69. Nakanishi T, Sugawara M, Huang W, Martindale RG, Leibach FH, Ganapathy ME, Prasad PD, Ganapathy V (2001) Structure, function, and tissue expression pattern of human SN2, a subtype of the amino acid transport system N. Biochem Biophys Res Commun 281:1343–1348

    Article  PubMed  Google Scholar 

  70. Nelson DM, Smith SD, Furesz TC, Sadovsky Y, Ganapathy V, Parvin CA, Smith CH (2003) Hypoxia reduces expression and function of system A amino acid transporters in cultured term human trophoblasts. Am J Physiol 284:C310–C315

    CAS  Google Scholar 

  71. Olalla L, Gutierrez A, Campos JA, Khan ZU, Alonso FJ, Segura JA, Marquez J, Aledo JC (2002) Nuclear localization of L-type glutaminase in mammalian brain. J Biol Chem 277:38939–38944

    Article  PubMed  Google Scholar 

  72. Oxender DL, Christensen HN (1963) Distinct mediating systems for the transport of neutral amino acids by the Ehrlich cell. J Biol Chem 238:3686–3699

    CAS  Google Scholar 

  73. Page RDM (1996) TreeView: an application to display phylogenetic trees on personal computers. Comput Appl Biosci 12:357–358

    CAS  PubMed  Google Scholar 

  74. Phillis JW, Ren J, O'Regan MH (2001) Studies on the effects of lactate transport inhibition, pyruvate, glucose and glutamine on amino acid, lactate and glucose release from the ischemic rat cerebral cortex. J Neurochem 76:247–257

    Article  PubMed  Google Scholar 

  75. Pow DV, Robinson SR (1994) Glutamate in some retinal neurons is derived solely from glia. Neuroscience 60:355–366

    Google Scholar 

  76. Reimer RJ, Chaudhry FA, Gray AT, Edwards RH (2000) Amino acid transport system A resembles system N in sequence but differs in mechanism. Proc Natl Acad Sci USA 97:7715–7720

    CAS  PubMed  Google Scholar 

  77. Rennie MJ, Bowtell JL, Bruce M, Khogali SEO (2001) Interaction between glutamine availability and metabolism of glycogen, tricarboxylic acid cycle intermediates and glutathione. J Nutr 131:2488S–2490S

    PubMed  Google Scholar 

  78. Rothman DL, Behar KL, Hyder F, Shulman RG (2003) In vivo NMR studies of the neurotransmitter flux and neuroenergetics: implications for brain function. Annu Rev Physiol 65:401–427

    Article  PubMed  Google Scholar 

  79. Russnak R, Konczal D, McIntire SL (2001) A family of yeast proteins mediating bidirectional vacuolar amino acid transport. J Biol Chem 276:23849–23857

    Article  CAS  PubMed  Google Scholar 

  80. Sagné C, El Mestikawy S, Isambert MF, Hamon M, Henry JP, Giros B, Gasnier B (1997) Cloning of a functional vesicular GABA and glycine transporter by screening of genome databases. FEBS Lett 417:177–183

    Article  PubMed  Google Scholar 

  81. Saier MH, Daniels GA, Boerner P, Lin J (1988) Neutral amino acid transport systems in animal cells: potential targets of oncogene action and regulators of cellular growth. J Membr Biol 104:1–20

    CAS  PubMed  Google Scholar 

  82. Shotwell MA, Jayme DW, Kilberg MS, Oxender DL (1981) Neutral amino acid transport systems in Chinese hamster ovary cells. J Biol Chem 256:5422–5427

    PubMed  Google Scholar 

  83. Sonnewald U, Westergaard N, Schousboe A, Svendsen JS, Unsgard G, Petersen SB (1993) Direct demonstration by [13C]NMR spectroscopy that glutamine from astrocytes is a precursor for GABA synthesis in neurons. Neurochem Int 22:19–29

    Article  PubMed  Google Scholar 

  84. Su TZ, Campbell GW, Oxender DL (1997) Glutamine transport in cerebellar granule cells in culture. Brain Res 757:69–78

    CAS  PubMed  Google Scholar 

  85. Sugawara M, Nakanishi T, Fei YJ, Huang W, Ganapathy ME, Leibach FH, Ganapathy V (2000) Cloning of an amino acid transporter with functional characteristics and tissue expression pattern identical to that of System A. J Biol Chem 275:16473–16477

    CAS  PubMed  Google Scholar 

  86. Sugawara M, Nakanishi T, Fei Y-J, Martindale RG, Ganapathy ME, Leibach FH, Ganapathy V (2000) Structure and function of ATA3, a new subtype of amino acid transport system A, primarily expressed in the liver and skeletal muscle. Biochim Biophys Acta 1509:7–13

    CAS  PubMed  Google Scholar 

  87. Sutinen E, Jyrkkiö S, Grönroos T, Haaparanta M, Lehikoinen P, Någren K (2001) Biodistribution of [11C]methylaminoisobutyric acid, a tracer for PET studies on system A amino acid transport in vivo. Eur J Nucl Med 28:847–854

    Google Scholar 

  88. Takanaga H, Tokuda N, Ohtsuki S, Hosoya K, Terasaki T (2002) ATA2 is predominantly expressed as system A at the blood-brain barrier and acts as brain-to-blood efflux transport for L-proline. Mol Pharmacol 61:1289–1296

    Article  PubMed  Google Scholar 

  89. Tamarappoo BK, Raizada MK, Kilberg MS (1997) Identification of a System N-like Na+-dependent glutamine transport activity in rat brain neurons. J Neurochem 68:954–960

    CAS  PubMed  Google Scholar 

  90. Tatusova TA, Madden TL (1999) BLAST 2 Sequences, a new tool for comparing protein and nucleotide sequences. FEMS Microbiol Lett 174:247–250

    CAS  PubMed  Google Scholar 

  91. Taylor PM, Rennie MJ, Low SY (1999) Biomembrane transport and interorgan nutrient flows: the amino acids. In: Van Winkle LJ (ed) Biomembrane transport. Academic Press, San Diego, pp 295–325

  92. Tengholm A, Meyer T (2002) A PI3-kinase signaling code for insulin-triggered insertion of glucose transporters into the plasma membrane. Curr Biol 12:1871–1876

    Article  PubMed  Google Scholar 

  93. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680

    PubMed  Google Scholar 

  94. Torgner I, Kvamme E (1990) Synthesis of transmitter glutamate and the glial-neuron interrelationship. Mol Chem Neuropathol 12:11–17

    PubMed  Google Scholar 

  95. Trama J, Go WY, Ho SN (2002) The osmoprotective function of the NFAT5 transcription factor in T cell development and activation. J Immunol 169:5477–5488

    PubMed  Google Scholar 

  96. Varoqui H, Erickson JD (2002) Selective up-regulation of System A transporter mRNA in diabetic liver. Biochem Biophys Res Commun 290:903–908

    Article  PubMed  Google Scholar 

  97. Varoqui H, Zhu H, Yao D, Ming H, Erickson JD (2000) Cloning and functional identification of a neuronal glutamine transporter. J Biol Chem 275:4049–4054

    Article  PubMed  Google Scholar 

  98. Varoqui H, Schäfer MKH, 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 

  99. Wang H, Huang W, Sugawara M, Devoe LD, Leibach FH, Prasad PD, Ganapathy V (2000) Cloning and functional expression of ATA1, a subtype of amino acid transporter A, from human placenta. Biochem Biophys Res Commun 273:1175–1179

    Article  PubMed  Google Scholar 

  100. Yao D, Mackenzie B, Ming H, Varoqui H, Zhu H, Hediger MA, Erickson JD (2000) A novel System A isoform mediating Na+/neutral amino acid cotransport. J Biol Chem 275:22790–22797

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Membrane Biology Program and Renal Division, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA

    Bryan Mackenzie

  2. Neuroscience Center and Department of Pharmacology, Louisiana State University Health Sciences Center, 2020 Gravier Street (Suite D), New Orleans, LA 70112, USA

    Jeffrey D. Erickson

Authors
  1. Bryan Mackenzie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeffrey D. Erickson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Bryan Mackenzie or Jeffrey D. Erickson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mackenzie, B., Erickson, J.D. Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family. Pflugers Arch - Eur J Physiol 447, 784–795 (2004). https://doi.org/10.1007/s00424-003-1117-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-003-1117-9

Keywords

Search

Navigation