amino acid transport system a

Summary

Summary: A sodium-dependent neutral amino acid transporter that accounts for most of the sodium-dependent neutral amino acid uptake by mammalian cells. The preferred substrates for this transporter system include ALANINE; SERINE; and GLUTAMINE.

Top Publications

  1. Thongsong B, Subramanian R, Ganapathy V, Prasad P. Inhibition of amino acid transport system a by interleukin-1beta in trophoblasts. J Soc Gynecol Investig. 2005;12:495-503 pubmed
    ..study sought to investigate the influence of interleukin-1beta (IL-1beta) on the function of the amino acid transport system A in trophoblasts...
  2. Kusinski L, Stanley J, Dilworth M, Hirt C, Andersson I, Renshall L, et al. eNOS knockout mouse as a model of fetal growth restriction with an impaired uterine artery function and placental transport phenotype. Am J Physiol Regul Integr Comp Physiol. 2012;303:R86-93 pubmed publisher
    ..We further postulate that this mouse model demonstrates "uteroplacental hypoxia," providing a new framework for understanding the etiology of FGR in human pregnancy...
  3. Palii S, Thiaville M, Pan Y, Zhong C, Kilberg M. Characterization of the amino acid response element within the human sodium-coupled neutral amino acid transporter 2 (SNAT2) System A transporter gene. Biochem J. 2006;395:517-27 pubmed
    ..Chromatin immunoprecipitation analysis established in vivo that amino acid deprivation led to increased RNA polymerase II recruitment to the SNAT2 promoter. ..
  4. Yu W, Cong W, Zhang Y, Chen Y, Wang F, Yu G. Overexpression of ATA1/SLC38A1 predicts future recurrence and death in Chinese patients with hilar cholangiocarcinoma. J Surg Res. 2011;171:663-8 pubmed publisher
    ..ATA1 expression may be used to predict recurrence and death and can serve as a promising target for therapy of this malignancy. ..
  5. Jones H, Jansson T, Powell T. IL-6 stimulates system A amino acid transporter activity in trophoblast cells through STAT3 and increased expression of SNAT2. Am J Physiol Cell Physiol. 2009;297:C1228-35 pubmed publisher
  6. Desforges M, Mynett K, Jones R, Greenwood S, Westwood M, Sibley C, et al. The SNAT4 isoform of the system A amino acid transporter is functional in human placental microvillous plasma membrane. J Physiol. 2009;587:61-72 pubmed publisher
  7. Coan P, Angiolini E, Sandovici I, Burton G, Constancia M, Fowden A. Adaptations in placental nutrient transfer capacity to meet fetal growth demands depend on placental size in mice. J Physiol. 2008;586:4567-76 pubmed publisher
    ..Thus, this adaptability in placental phenotype provides a functional reserve capacity for maximizing fetal growth during late gestation when placental growth is compromised...
  8. Jones H, Ashworth C, Page K, McArdle H. Cortisol stimulates system A amino acid transport and SNAT2 expression in a human placental cell line (BeWo). Am J Physiol Endocrinol Metab. 2006;291:E596-603 pubmed
    ..It is also the first study to identify which system A isoform is regulated. These results suggest that cortisol may be involved in upregulation of system A in the placenta to ensure sufficient amino acid supply to the developing fetus. ..
  9. Ogura M, Nakamichi N, Takano K, Oikawa H, Kambe Y, Ohno Y, et al. Functional expression of A glutamine transporter responsive to down-regulation by lipopolysaccharide through reduced promoter activity in cultured rat neocortical astrocytes. J Neurosci Res. 2006;83:1447-60 pubmed

More Information

Publications62

  1. Yao D, Mackenzie B, Ming H, Varoqui H, Zhu H, Hediger M, et al. A novel system A isoform mediating Na+/neutral amino acid cotransport. J Biol Chem. 2000;275:22790-7 pubmed
  2. Desforges M, Lacey H, Glazier J, Greenwood S, Mynett K, Speake P, et al. SNAT4 isoform of system A amino acid transporter is expressed in human placenta. Am J Physiol Cell Physiol. 2006;290:C305-12 pubmed
    ..This study therefore provides the first evidence of SNAT4 mRNA and protein expression in the human placenta, both at the first trimester and at full term. ..
  3. Hyde R, Christie G, Litherland G, Hajduch E, Taylor P, Hundal H. Subcellular localization and adaptive up-regulation of the System A (SAT2) amino acid transporter in skeletal-muscle cells and adipocytes. Biochem J. 2001;355:563-8 pubmed
  4. Jansson T, Ylvén K, Wennergren M, Powell T. Glucose transport and system A activity in syncytiotrophoblast microvillous and basal plasma membranes in intrauterine growth restriction. Placenta. 2002;23:392-9 pubmed
    ..The hypoglycemia present in utero in some IUGR fetuses is not caused by a decreased glucose transport capacity across the syncytiotrophoblast plasma membranes. ..
  5. Takanaga H, Tokuda N, Ohtsuki S, Hosoya K, Terasaki T. 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. 2002;61:1289-96 pubmed
    ..The predominantly expressed ATA2 mRNA at the BBB may play a role in maintaining the concentration of small neutral amino acids and cerebral osmotic pressure in the brain under pathological conditions. ..
  6. Albers A, Bröer A, Wagner C, Setiawan I, Lang P, Kranz E, et al. Na+ transport by the neural glutamine transporter ATA1. Pflugers Arch. 2001;443:92-101 pubmed
    ..A decrease of the intracellular pH similarly inhibited glutamine transport via ATA1, suggesting that the pH dependence was an allosteric effect on the transporter. ..
  7. Alfieri R, Petronini P, Bonelli M, Caccamo A, Cavazzoni A, Borghetti A, et al. Osmotic regulation of ATA2 mRNA expression and amino acid transport System A activity. Biochem Biophys Res Commun. 2001;283:174-8 pubmed
    ..were exposed to hypertonicity, both the level of ATA2 (amino acid transporter 2) mRNA and activity of amino acid transport System A increased transiently, peaking after about 6 and 9 h, respectively...
  8. Hyde R, Peyrollier K, Hundal H. Insulin promotes the cell surface recruitment of the SAT2/ATA2 system A amino acid transporter from an endosomal compartment in skeletal muscle cells. J Biol Chem. 2002;277:13628-34 pubmed
    ..Our data indicate strongly that insulin increases System A transport in L6 cells by stimulating the exocytosis of SAT2 carriers from a chloroquine-sensitive endosomal compartment. ..
  9. Ogura M, Takarada T, Nakamichi N, Kawagoe H, Sako A, Nakazato R, et al. Exacerbated vulnerability to oxidative stress in astrocytic C6 glioma cells with stable overexpression of the glutamine transporter slc38a1. Neurochem Int. 2011;58:504-11 pubmed publisher
    ..These results suggest that GlnT may play a role in the mechanisms underlying the determination of cellular viability in astrocytes through modulation of intracellular ROS generation. ..
  10. Novak D, Lehman M, Bernstein H, Beveridge M, Cramer S. SNAT expression in rat placenta. Placenta. 2006;27:510-6 pubmed
    b>Amino acid transport System A (SysA) activity is present within the rodent and human placentas. Inhibition of this transport system is associated with fetal growth retardation...
  11. Ogura M, Taniura H, Nakamichi N, Yoneda Y. Upregulation of the glutamine transporter through transactivation mediated by cAMP/protein kinase A signals toward exacerbation of vulnerability to oxidative stress in rat neocortical astrocytes. J Cell Physiol. 2007;212:375-85 pubmed
    ..These results suggest that GlnT expression is upregulated by cAMP/PKA signals for subsequent exacerbation of the vulnerability to oxidative stress in astrocytes. ..
  12. Ericsson A, Hamark B, Jansson N, Johansson B, Powell T, Jansson T. Hormonal regulation of glucose and system A amino acid transport in first trimester placental villous fragments. Am J Physiol Regul Integr Comp Physiol. 2005;288:R656-62 pubmed
    ..In contrast to term placental villous fragments, system A activity was not regulated by insulin or leptin in first trimester but was downregulated by GH. ..
  13. Zaitoun I, Khatib H. Assessment of genomic imprinting of SLC38A4, NNAT, NAP1L5, and H19 in cattle. BMC Genet. 2006;7:49 pubmed
    ..It is of interest that the imprinting of NAP1L5, NNAT, and H19 appears to be conserved between mouse and cow, although the tissue distribution of expression differs. In contrast, the imprinting of SLC38A4 appears to be species-specific. ..
  14. Palii S, Chen H, Kilberg M. Transcriptional control of the human sodium-coupled neutral amino acid transporter system A gene by amino acid availability is mediated by an intronic element. J Biol Chem. 2004;279:3463-71 pubmed
    ..The SNAT2 AARE, along with a nearby conserved CAAT box, has enhancer activity in that it functions in an orientation and position independent manner, and it confers regulated transcription to a heterologous promoter. ..
  15. Hatanaka T, Hatanaka Y, Tsuchida J, Ganapathy V, Setou M. Amino acid transporter ATA2 is stored at the trans-Golgi network and released by insulin stimulus in adipocytes. J Biol Chem. 2006;281:39273-84 pubmed
    Recently, we cloned the ATA/SNAT transporters responsible for amino acid transport system A. System A is one of the major transport systems for small neutral and glucogenic amino acids represented by alanine and is involved in the ..
  16. Mackenzie B, Erickson J. Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family. Pflugers Arch. 2004;447:784-95 pubmed
    ..Probing their regulation has revealed additional roles, and recent work has considered SLC38 transporters as therapeutic targets in neoplasia. ..
  17. L pez Fontanals M, Rodr guez Mulero S, Casado F, D rijard B, Pastor Anglada M. The osmoregulatory and the amino acid-regulated responses of system A are mediated by different signal transduction pathways. J Gen Physiol. 2003;122:5-16 pubmed publisher
    ..The involvement of a CDK-cyclin complex in the osmotic response of system A links the activity of this transporter to the increase in cell volume previous to the entry in a new cell division cycle...
  18. Melone M, Varoqui H, Erickson J, Conti F. Localization of the Na(+)-coupled neutral amino acid transporter 2 in the cerebral cortex. Neuroscience. 2006;140:281-92 pubmed
  19. Cramer S, Beveridge M, Kilberg M, Novak D. Physiological importance of system A-mediated amino acid transport to rat fetal development. Am J Physiol Cell Physiol. 2002;282:C153-60 pubmed
    ..55 +/- 0.04 g (n = 113), experimental group: -3.29 +/- 0.04 g (n = 128)], implying an integral role for system A transport in fetal growth and development in the rat. ..
  20. Audette M, Greenwood S, Sibley C, Jones C, Challis J, Matthews S, et al. Dexamethasone stimulates placental system A transport and trophoblast differentiation in term villous explants. Placenta. 2010;31:97-105 pubmed publisher
    ..05 for all)) markers of syncytiotrophoblast differentiation. These findings suggest that DEX stimulates system A activity and promotes syncytiotrophoblast differentiation and maturation. ..
  21. Jansson N, Greenwood S, Johansson B, Powell T, Jansson T. Leptin stimulates the activity of the system A amino acid transporter in human placental villous fragments. J Clin Endocrinol Metab. 2003;88:1205-11 pubmed
    ..We conclude that primary single isolated villous fragments can be used in studies of hormonal regulation of nutrient uptake into the syncytiotrophoblast. These data suggest that leptin regulates system A, a key amino acid transporter. ..
  22. Zhang Z, Grewer C. The sodium-coupled neutral amino acid transporter SNAT2 mediates an anion leak conductance that is differentially inhibited by transported substrates. Biophys J. 2007;92:2621-32 pubmed
    ..Therefore, we can speculate that such anion-conducting pathways are general features of Na+-transporting systems. ..
  23. Armano S, Coco S, Bacci A, Pravettoni E, Schenk U, Verderio C, et al. Localization and functional relevance of system a neutral amino acid transporters in cultured hippocampal neurons. J Biol Chem. 2002;277:10467-73 pubmed
  24. Fricke M, Jones Davis D, Mathews G. Glutamine uptake by System A transporters maintains neurotransmitter GABA synthesis and inhibitory synaptic transmission. J Neurochem. 2007;102:1895-1904 pubmed publisher
    ..However, in contrast to glutamate, extracellular glutamine levels are normally high. Therefore, we propose a supportive role for glutamine, even under resting conditions, to maintain GABA vesicle filling. ..
  25. Buntup D, Skare O, Solbu T, Chaudhry F, Storm Mathisen J, Thangnipon W. Beta-amyloid 25-35 peptide reduces the expression of glutamine transporter SAT1 in cultured cortical neurons. Neurochem Res. 2008;33:248-56 pubmed
    ..The results indicate that Abeta may impair neuronal function and transmitter synthesis, and perhaps reduce excitotoxicity, through a reduction in neuronal glutamine uptake. ..
  26. Chaudhry F, Schmitz D, Reimer R, Larsson P, Gray A, Nicoll R, et al. Glutamine uptake by neurons: interaction of protons with system a transporters. J Neurosci. 2002;22:62-72 pubmed
    ..Differences between System N and A transporters in coupling to H+ thus contribute to the delivery of glutamine from glia to neurons. Nonetheless, although they are not transported, H+ inhibit SA1 and SA2 by competing with Na+. ..
  27. Jenstad M, Quazi A, Zilberter M, Haglerød C, Berghuis P, Saddique N, et al. System A transporter SAT2 mediates replenishment of dendritic glutamate pools controlling retrograde signaling by glutamate. Cereb Cortex. 2009;19:1092-106 pubmed publisher
    ..In summary, we demonstrate that SAT2 maintains a key metabolic glutamine/glutamate balance underpinning retrograde signaling by dendritic release of the neurotransmitter glutamate. ..
  28. Baird F, Bett K, MacLean C, Tee A, Hundal H, Taylor P. Tertiary active transport of amino acids reconstituted by coexpression of System A and L transporters in Xenopus oocytes. Am J Physiol Endocrinol Metab. 2009;297:E822-9 pubmed publisher
    ..5 nmol/oocyte). The observed changes in Leu accumulation are sufficient to activate the TOR pathway in oocytes, although intracellular AA metabolism limits the potential for AA accumulation by tertiary active transport in this system. ..
  29. Varoqui H, Erickson J. Selective up-regulation of system a transporter mRNA in diabetic liver. Biochem Biophys Res Commun. 2002;290:903-8 pubmed
    ..These results indicate that the increase in system A activity observed in liver following experimentally induced diabetes or glucagon treatment is due to the selective increase in mRNAs encoding system A transporters. ..
  30. Mizuno Y, Sotomaru Y, Katsuzawa Y, Kono T, Meguro M, Oshimura M, et al. Asb4, Ata3, and Dcn are novel imprinted genes identified by high-throughput screening using RIKEN cDNA microarray. Biochem Biophys Res Commun. 2002;290:1499-505 pubmed
    ..The 25 candidates also included genes that showed no imprinting-associated expression in normal diploid embryos. We describe a feasible high-throughput method of screening for novel imprinted genes by using the RIKEN cDNA microarray. ..
  31. Constancia M, Angiolini E, Sandovici I, Smith P, Smith R, Kelsey G, et al. Adaptation of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter systems. Proc Natl Acad Sci U S A. 2005;102:19219-24 pubmed
    ..Thus, crosstalk between an imprinted growth demand gene (Igf2) and placental supply transporter genes (Slc38a4, Slc38a2, and Slc2a3) may be a component of the genetic control of nutrient supply and demand during mammalian development. ..
  32. Pastor Anglada M, Derijard B, Casado F. Mechanisms implicated in the response of system a to hypertonic stress and amino acid deprivation still can be different. J Gen Physiol. 2005;125:41-2 pubmed
  33. Trama J, Go W, Ho S. The osmoprotective function of the NFAT5 transcription factor in T cell development and activation. J Immunol. 2002;169:5477-88 pubmed
  34. Smith R, Dean W, Konfortova G, Kelsey G. Identification of novel imprinted genes in a genome-wide screen for maternal methylation. Genome Res. 2003;13:558-69 pubmed
    ..Interestingly, two of the three novel genes identified in this screen are located within the introns of other genes; their identification indicates that such "microimprinted" domains may be more common than previously thought. ..
  35. Bain P, LeBlanc Chaffin R, Chen H, Palii S, Leach K, Kilberg M. The mechanism for transcriptional activation of the human ATA2 transporter gene by amino acid deprivation is different than that for asparagine synthetase. J Nutr. 2002;132:3023-9 pubmed
  36. Jones H, Ashworth C, Page K, McArdle H. Expression and adaptive regulation of amino acid transport system A in a placental cell line under amino acid restriction. Reproduction. 2006;131:951-60 pubmed
    ..These data have shown that placental cells adapt in vitro to nutritional stress and have identified the physiological, biochemical and genomic mechanisms involved. ..
  37. Nelson D, Smith S, Furesz T, Sadovsky Y, Ganapathy V, Parvin C, et al. Hypoxia reduces expression and function of system A amino acid transporters in cultured term human trophoblasts. Am J Physiol Cell Physiol. 2003;284:C310-5 pubmed
    ..Hypoxia decreased expression of hATA1 and hATA2 in both trophoblast phenotypes. We conclude that hypoxia downregulates system A transporter expression and activity in cultured human trophoblasts. ..
  38. Mackenzie B, Schafer M, Erickson J, Hediger M, Weihe E, Varoqui H. Functional properties and cellular distribution of the system A glutamine transporter SNAT1 support specialized roles in central neurons. J Biol Chem. 2003;278:23720-30 pubmed
  39. Dolinska M, Zabłocka B, Sonnewald U, Albrecht J. Glutamine uptake and expression of mRNA's of glutamine transporting proteins in mouse cerebellar and cerebral cortical astrocytes and neurons. Neurochem Int. 2004;44:75-81 pubmed
    ..System N-mediated (threonine+MeAiB-inhibitable) Gln uptake showed comparable activities in all four types of cells, which is compatible with the ubiquitous expression of NAT2 mRNA-a mouse brain-specific N-system isoform. ..
  40. Sundberg B, Wååg E, Jacobsson J, Stephansson O, Rumaks J, Svirskis S, et al. The evolutionary history and tissue mapping of amino acid transporters belonging to solute carrier families SLC32, SLC36, and SLC38. J Mol Neurosci. 2008;35:179-93 pubmed publisher
    ..In addition, we performed a detailed expression analysis of SLC38A1 and SLC38A6 in mouse brain using in situ hybridization, which showed that both these transporters are widely expressed in the brain. ..
  41. Sidoryk M, Matyja E, Dybel A, Zielinska M, Bogucki J, Jaskolski D, et al. Increased expression of a glutamine transporter SNAT3 is a marker of malignant gliomas. Neuroreport. 2004;15:575-8 pubmed
    ..The expression of ASCT2 mRNA, but not SNAT5 or SNAT1 mRNAs, was increased in all neoplastic tissues studied. Hence, increased expression of SNAT3 is a marker of primary malignant gliomas in situ. ..
  42. Kondoh N, Imazeki N, Arai M, Hada A, Hatsuse K, Matsuo H, et al. Activation of a system A amino acid transporter, ATA1/SLC38A1, in human hepatocellular carcinoma and preneoplastic liver tissues. Int J Oncol. 2007;31:81-7 pubmed
    ..SiRNA-mediated suppression of endogenous ATA1 lowered the viability of HepG2 cells. Thus, the activation of ATA1 confers growth and survival advantages in pre-malignant and malignant liver lesions. ..
  43. Kanamori K, Ross B. Quantitative determination of extracellular glutamine concentration in rat brain, and its elevation in vivo by system A transport inhibitor, alpha-(methylamino)isobutyrate. J Neurochem. 2004;90:203-10 pubmed
  44. Burkhalter J, Fiumelli H, Erickson J, Martin J. A critical role for system A amino acid transport in the regulation of dendritic development by brain-derived neurotrophic factor (BDNF). J Biol Chem. 2007;282:5152-9 pubmed
  45. Srinivas S, Prasad P, Umapathy N, Ganapathy V, Shekhawat P. Transport of butyryl-L-carnitine, a potential prodrug, via the carnitine transporter OCTN2 and the amino acid transporter ATB(0,+). Am J Physiol Gastrointest Liver Physiol. 2007;293:G1046-53 pubmed
    ..5), 0.40 +/- 0.02 microM). We conclude that ATB(0,+) is a low-affinity/high-capacity transporter for BC, whereas OCTN2 is a high-affinity/low-capacity transporter. ATB(0,+) may mediate intestinal absorption of BC when OCTN2 is defective. ..
  46. Gómez T, Medina V, Ramírez C, Dópido R, Lorenzo A, Diaz M. Regulation of L-alanine transport systems A and ASC by cyclic AMP and calcium in a reptilian duodenal model. J Exp Biol. 2003;206:1589-98 pubmed
    ..The different sensitivity exhibited by individual transport pathways may well account for the changes observed in overall alanine transport. ..
  47. Okamoto M, Akanuma S, Tachikawa M, Hosoya K. Characteristics of glycine transport across the inner blood-retinal barrier. Neurochem Int. 2009;55:789-95 pubmed publisher
    ..In conclusion, GlyT1 most likely mediates glycine transport at the inner BRB and is expected to play an important role in regulating the glycine concentration in the neural retina. ..
  48. Regnault T, de Vrijer B, Anthony R. The IGF-II-deficient placenta: aspects of its function. Trends Endocrinol Metab. 2002;13:410-2 pubmed
  49. Hosoya K, Ichikawa T, Akanuma S, Hirose S, Tachikawa M. Glycine and L-arginine transport in cultured Müller glial cells (TR-MUL). Neurochem Int. 2010;57:262-8 pubmed publisher
    ..In conclusion, GlyT1 and CAT1 most likely mediate glycine and L-arginine uptake, respectively, by Müller cells and are expected to play an important role in supplying precursors for creatine biosynthesis in Müller cells. ..
  50. King N, Lin H, Suleiman M. Oxidative stress increases SNAT1 expression and stimulates cysteine uptake in freshly isolated rat cardiomyocytes. Amino Acids. 2011;40:517-26 pubmed publisher
    ..In conclusion, under control conditions SNAT transporters aid in the delivery of cysteine for cardiomyocyte GSH synthesis, whilst oxidative stress increases cardiomyocyte cysteine uptake and stimulates cardiomyocyte SNAT1 expression. ..
  51. Alfieri R, Bonelli M, Petronini P, Borghetti A. Stabilization of hsp70 mRNA on prolonged cell exposure to hypertonicity. Biochim Biophys Acta. 2002;1592:135-40 pubmed
    ..These findings suggest that hypertonic treatment increases the production of hsp70 protein in 3T3 cells via a stabilization of its corresponding mRNA. ..
  52. Hamdi M, Mutungi G. Dihydrotestosterone stimulates amino acid uptake and the expression of LAT2 in mouse skeletal muscle fibres through an ERK1/2-dependent mechanism. J Physiol. 2011;589:3623-40 pubmed publisher
    ..This effect is mediated through the EGFR and involves the activation of the MAPK pathway and an increase in LAT2 expression. ..
  53. Warrander L, Batra G, Bernatavicius G, Greenwood S, Dutton P, Jones R, et al. Maternal perception of reduced fetal movements is associated with altered placental structure and function. PLoS ONE. 2012;7:e34851 pubmed publisher
    ..This suggests that women presenting with RFM require further investigation to identify those with placental insufficiency. ..