amino acid transport system asc

Summary

Summary: A ubiquitous sodium-dependent neutral amino acid transporter. The preferred substrates for this transporter system include ALANINE; SERINE; and CYSTEINE.

Top Publications

  1. Albers T, Marsiglia W, Thomas T, Gameiro A, Grewer C. Defining substrate and blocker activity of alanine-serine-cysteine transporter 2 (ASCT2) Ligands with Novel Serine Analogs. Mol Pharmacol. 2012;81:356-65 pubmed publisher
    ..An aromatic residue in the side chain is required for high-affinity interaction. One of the compounds, the l-serine ester serine biphenyl-4-carboxylate reversibly inhibits ASCT2 function with an apparent affinity of 30 ?M. ..
  2. Lavillette D, Marin M, Ruggieri A, Mallet F, Cosset F, Kabat D. The envelope glycoprotein of human endogenous retrovirus type W uses a divergent family of amino acid transporters/cell surface receptors. J Virol. 2002;76:6442-52 pubmed
    ..The recognition of ASCT1 and ASCT2 despite this divergence of their sequences strongly suggests that the use of both receptors has been highly advantageous for survival and evolution of the HERV-W family of retroviruses. ..
  3. Skowronek M, Georgi A, Jamra R, Schumacher J, Becker T, Schmael C, et al. No association between genetic variants at the ASCT1 gene and schizophrenia or bipolar disorder in a German sample. Psychiatr Genet. 2006;16:233-4 pubmed
    ..Allele and haplotype frequencies did not differ between cases and controls. Our results do not support an association of the ASCT1 gene with BD or SCZ in the German population. ..
  4. Sakai K, Shimizu H, Koike T, Furuya S, Watanabe M. Neutral amino acid transporter ASCT1 is preferentially expressed in L-Ser-synthetic/storing glial cells in the mouse brain with transient expression in developing capillaries. J Neurosci. 2003;23:550-60 pubmed
    ..Therefore, ASCT1 appears to be regulated to meet metabolic demands by differentiating and mature neurons through the transport of glia- and blood-borne small neutral amino acids. ..
  5. Cheynet V, Oriol G, Mallet F. Identification of the hASCT2-binding domain of the Env ERVWE1/syncytin-1 fusogenic glycoprotein. Retrovirology. 2006;3:41 pubmed
  6. Tailor C, Nouri A, Zhao Y, Takeuchi Y, Kabat D. A sodium-dependent neutral-amino-acid transporter mediates infections of feline and baboon endogenous retroviruses and simian type D retroviruses. J Virol. 1999;73:4470-4 pubmed
    ..The human Bo transporter gene has been previously mapped to 19q13.3, which is closely linked to the gene locus of the RD114 receptor...
  7. Shao Z, Kamboj A, Anderson C. Functional and immunocytochemical characterization of D-serine transporters in cortical neuron and astrocyte cultures. J Neurosci Res. 2009;87:2520-30 pubmed publisher
    ..Together these findings further our knowledge of the processes that govern D-serine regulation. ..
  8. Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, et al. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 2009;136:521-34 pubmed publisher
    ..Thus, L-glutamine flux regulates mTOR, translation and autophagy to coordinate cell growth and proliferation. ..
  9. Rasko J, Battini J, Gottschalk R, Mazo I, Miller A. The RD114/simian type D retrovirus receptor is a neutral amino acid transporter. Proc Natl Acad Sci U S A. 1999;96:2129-34 pubmed

More Information

Publications62

  1. Weis S, Llenos I, Dulay J, Verma N, Sabunciyan S, Yolken R. Changes in region- and cell type-specific expression patterns of neutral amino acid transporter 1 (ASCT-1) in the anterior cingulate cortex and hippocampus in schizophrenia, bipolar disorder and major depression. J Neural Transm (Vienna). 2007;114:261-71 pubmed
  2. Fuchs B, Bode B. Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime?. Semin Cancer Biol. 2005;15:254-66 pubmed
  3. Grewer C, Grabsch E. New inhibitors for the neutral amino acid transporter ASCT2 reveal its Na+-dependent anion leak. J Physiol. 2004;557:747-59 pubmed
  4. Yamamoto T, Nishizaki I, Nukada T, Kamegaya E, Furuya S, Hirabayashi Y, et al. Functional identification of ASCT1 neutral amino acid transporter as the predominant system for the uptake of L-serine in rat neurons in primary culture. Neurosci Res. 2004;49:101-11 pubmed
    ..Taken together, these findings indicate that ASCT1 predominantly contributes to the uptake of L-serine in primary neurons. ..
  5. Deitmer J, Bröer A, Broer S. Glutamine efflux from astrocytes is mediated by multiple pathways. J Neurochem. 2003;87:127-35 pubmed
  6. Weiss M, Derazi S, Kilberg M, Anderson K. Ontogeny and localization of the neutral amino acid transporter ASCT1 in rat brain. Brain Res Dev Brain Res. 2001;130:183-90 pubmed
    ..In addition, the expression and localization of ASCT1 are consistent with its possible role in pathophysiological processes that involve glutamate toxicity. ..
  7. Dolinska M, Dybel A, Hilgier W, Zielinska M, Zabłocka B, Buzanska L, et al. Glutamine transport in C6 glioma cells: substrate specificity and modulation in a glutamine deprived culture medium. J Neurosci Res. 2001;66:959-66 pubmed
    ..The N system-mediated uptake in C6 cells grown in the absence, but not in the presence of Gln was not inhibited by glutamate (Glu) that conforms to the characteristics of the glial N system variant, SN1. ..
  8. Witte D, Ali N, Carlson N, Younes M. Overexpression of the neutral amino acid transporter ASCT2 in human colorectal adenocarcinoma. Anticancer Res. 2002;22:2555-7 pubmed
    ..Larger studies with multivariate analysis are needed to determine whether ASCT2 expression is an independent prognostic marker in CRC. ..
  9. Esslinger C, Cybulski K, Rhoderick J. Ngamma-aryl glutamine analogues as probes of the ASCT2 neutral amino acid transporter binding site. Bioorg Med Chem. 2005;13:1111-8 pubmed
    ..Through this study a preliminary binding site map has been developed, and a potent commercially available competitive inhibitor of the ASCT2 transporter has been identified. ..
  10. Lim J, Li L, Jacobs M, Kistler J, Donaldson P. Mapping of glutathione and its precursor amino acids reveals a role for GLYT2 in glycine uptake in the lens core. Invest Ophthalmol Vis Sci. 2007;48:5142-51 pubmed
    ..Enhancing the delivery of glycine to the core via the sutures may represent a pathway to protect the lens against the protein modifications associated with age-related nuclear cataract. ..
  11. Okudaira H, Nakanishi T, Oka S, Kobayashi M, Tamagami H, Schuster D, et al. Kinetic analyses of trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid transport in Xenopus laevis oocytes expressing human ASCT2 and SNAT2. Nucl Med Biol. 2013;40:670-5 pubmed publisher
    ..Anti-FACBC has higher affinity for ASCT2 than for SNAT2, LAT1, or LAT2. The ASCT2-preferential transport of anti-[(18)F]FACBC in cancer cells could be used for more effective prostate cancer imaging. ..
  12. Chen C, Wang K, Chen C, Yu C, Chuang H, Chen H. Altered placental syncytin and its receptor ASCT2 expression in placental development and pre-eclampsia. BJOG. 2006;113:152-8 pubmed
    ..Correspondingly, hypoxia decreases syncytin but not ASCT2 gene expression in cultured cytotrophoblasts. ..
  13. Maucler C, Pernot P, Vasylieva N, Pollegioni L, Marinesco S. In vivo D-serine hetero-exchange through alanine-serine-cysteine (ASC) transporters detected by microelectrode biosensors. ACS Chem Neurosci. 2013;4:772-81 pubmed publisher
    ..Together, these results indicate that D-serine heteroexchange through ASC transporters is present in vivo and may constitute a key component in the regulation of D-serine extracellular concentration. ..
  14. Kim S, Kim D, Jung W, Koo J. Expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer. Endocr Relat Cancer. 2013;20:339-48 pubmed publisher
    ..001) expression. We identified differential expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer. The highest glutamine metabolic activity was seen in HER2-type breast cancer. ..
  15. Okudaira H, Shikano N, Nishii R, Miyagi T, Yoshimoto M, Kobayashi M, et al. Putative transport mechanism and intracellular fate of trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid in human prostate cancer. J Nucl Med. 2011;52:822-9 pubmed publisher
    ..Moreover, (14)C-FACBC is not incorporated into proteins in cells. These findings suggest a possible mechanism of anti-(18)F-FACBC PET for prostate cancer. ..
  16. Hassanein M, Hoeksema M, Shiota M, Qian J, Harris B, Chen H, et al. SLC1A5 mediates glutamine transport required for lung cancer cell growth and survival. Clin Cancer Res. 2013;19:560-70 pubmed publisher
    ..These results suggest that SLC1A5 plays a key role in Gln transport controlling lung cancer cells' metabolism, growth, and survival. ..
  17. Fuchs B, Finger R, Onan M, Bode B. ASCT2 silencing regulates mammalian target-of-rapamycin growth and survival signaling in human hepatoma cells. Am J Physiol Cell Physiol. 2007;293:C55-63 pubmed
    ..These results suggest that ASCT2 silencing inhibits mTORC1 signaling to the translational machinery followed by an mTORC2-initiated survival response, establishing a link between amino acid transporter expression and mTOR function. ..
  18. Scopelliti A, Ryan R, Vandenberg R. Molecular determinants for functional differences between alanine-serine-cysteine transporter 1 and other glutamate transporter family members. J Biol Chem. 2013;288:8250-7 pubmed publisher
    ..5; however, this was reversed by the additional mutation A382T. We propose that these residues differences in TM7 and TM8 combine to determine differences in substrate selectivity between members of the SLC1 family. ..
  19. Nano J, Ghanbari M, Wang W, de Vries P, Dhana K, Muka T, et al. Epigenome-Wide Association Study Identifies Methylation Sites Associated With Liver Enzymes and Hepatic Steatosis. Gastroenterology. 2017;153:1096-1106.e2 pubmed publisher
    ..Our results provide new insights into epigenetic mechanisms associated with markers of liver function and hepatic steatosis, laying the groundwork for future diagnostic and therapeutic applications. ..
  20. Tetsuka K, Takanaga H, Ohtsuki S, Hosoya K, Terasaki T. The l-isomer-selective transport of aspartic acid is mediated by ASCT2 at the blood-brain barrier. J Neurochem. 2003;87:891-901 pubmed
    ..Moreover, immunohistochemical analysis suggests that ASCT2 is localized at the abluminal side of the mouse BBB. These results suggest that ASCT2 plays a key role in l-isomer-selective Asp efflux transport at the BBB. ..
  21. Potter S, Lu A, Wilcken B, Green K, Rasko J. Hartnup disorder: polymorphisms identified in the neutral amino acid transporter SLC1A5. J Inherit Metab Dis. 2002;25:437-48 pubmed
    ..In the six unrelated Hartnup pedigrees studied, examination of linkage at 19q13.3, polymorphisms in the coding sequence and quantitation of expression of SLC1A5 did not suffice to explain the defect in neutral amino acid transport...
  22. Büdy B, O Neill R, DiBello P, Sengupta S, Jacobsen D. Homocysteine transport by human aortic endothelial cells: identification and properties of import systems. Arch Biochem Biophys. 2006;446:119-30 pubmed
    ..A similar pattern was observed for [35S]L-cysteine. Thus, L-homocysteine and L-homocystine found in hyperhomocysteinemic subjects can gain entry into the vascular endothelium by way of multiple L-cysteine transporters. ..
  23. Kudo Y, Boyd C, Sargent I, Redman C. Hypoxia alters expression and function of syncytin and its receptor during trophoblast cell fusion of human placental BeWo cells: implications for impaired trophoblast syncytialisation in pre-eclampsia. Biochim Biophys Acta. 2003;1638:63-71 pubmed
  24. Poffenberger M, Jones R. Amino acids fuel T cell-mediated inflammation. Immunity. 2014;40:635-7 pubmed publisher
    ..In this issue of Immunity, Nakaya et al. (2014) report that the glutamine transporter ASCT2 regulates T cell metabolism and mTOR kinase signaling to shape inflammatory T helper cell responses. ..
  25. Pötgens A, Drewlo S, Kokozidou M, Kaufmann P. Syncytin: the major regulator of trophoblast fusion? Recent developments and hypotheses on its action. Hum Reprod Update. 2004;10:487-96 pubmed
    ..In some of the hypotheses proposed, local coexpression of syncytin and receptor, leading to blocking of one factor by the other, is of functional relevance. ..
  26. Furuya S, Watanabe M. Novel neuroglial and glioglial relationships mediated by L-serine metabolism. Arch Histol Cytol. 2003;66:109-21 pubmed
    ..A transient capillary expression of ASCT1 in fetal and neonatal brains further suggests that, in addition to the glia-borne L-serine, an active transport of blood-borne L-serine would play an essential role in neural development. ..
  27. Sugimoto J, Sugimoto M, BERNSTEIN H, Jinno Y, Schust D. A novel human endogenous retroviral protein inhibits cell-cell fusion. Sci Rep. 2013;3:1462 pubmed publisher
    ..Identification of the first host cell-encoded inhibitor of mammalian cell fusion may encourage improved understanding of cell fusion mechanisms, of placental morphogenesis and of diseases resulting from abnormal cell fusion. ..
  28. Bjersand K, Seidal T, Sundström Poromaa I, Akerud H, Skirnisdottir I. The clinical and prognostic correlation of HRNPM and SLC1A5 in pathogenesis and prognosis in epithelial ovarian cancer. PLoS ONE. 2017;12:e0179363 pubmed publisher
    ..In patients with non-serous ovarian cancer SLC1A5 protects from recurrent disease, presumably by means of biological mechanisms that are unrelated to cytotoxic drug sensitivity. ..
  29. Laval J, Touhami J, Herzenberg L, Conrad C, Taylor N, Battini J, et al. Metabolic adaptation of neutrophils in cystic fibrosis airways involves distinct shifts in nutrient transporter expression. J Immunol. 2013;190:6043-50 pubmed publisher
    ..Thus, neutrophils recruited from blood into the CF airway lumen display augmented cell surface nutrient transporter expression and glucose uptake, consistent with metabolic adaptation. ..
  30. Toyoda M, Kaira K, Ohshima Y, Ishioka N, Shino M, Sakakura K, et al. Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer. Br J Cancer. 2014;110:2506-13 pubmed publisher
    ..L-type amino-acid transporter 1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may have an important role in the development and aggressiveness of tongue cancer. ..
  31. Oppedisano F, Catto M, Koutentis P, Nicolotti O, Pochini L, Koyioni M, et al. Inactivation of the glutamine/amino acid transporter ASCT2 by 1,2,3-dithiazoles: proteoliposomes as a tool to gain insights in the molecular mechanism of action and of antitumor activity. Toxicol Appl Pharmacol. 2012;265:93-102 pubmed publisher
    ..Indeed, computational studies using a homology structural model of ASCT2 transporter, suggested as possible binding targets, Cys-207 or Cys-210, that belong to the CXXC motif of the protein. ..
  32. Barel M, Meibom K, Dubail I, Botella J, Charbit A. Francisella tularensis regulates the expression of the amino acid transporter SLC1A5 in infected THP-1 human monocytes. Cell Microbiol. 2012;14:1769-83 pubmed publisher
    ..Our results are the first, which show that Francisella intracellular multiplication in human monocyte cytoplasm is associated with a post-translational modification of a eukaryotic amino acid transporter...
  33. Dunk C, Gellhaus A, Drewlo S, Baczyk D, Pötgens A, Winterhager E, et al. The molecular role of connexin 43 in human trophoblast cell fusion. Biol Reprod. 2012;86:115 pubmed publisher
    ..We conclude that Cx43-mediated GJIC and SLC1A5 interaction play important functional roles in trophoblast cell fusion. ..
  34. Pinho M, Serrão M, Soares da Silva P. High-salt intake and the renal expression of amino acid transporters in spontaneously hypertensive rats. Am J Physiol Renal Physiol. 2007;292:F1452-63 pubmed
  35. Pinto V, Pinho M, Jose P, Soares da Silva P. Role of H(2)O(2) on the kinetics of low-affinity high-capacity Na(+)-dependent alanine transport in SHR proximal tubular epithelial cells. Biochem Biophys Res Commun. 2010;398:553-8 pubmed publisher
    ..It is suggested that Na(+) binding in renal ASCT2 may be regulated by ROS in SHR PTE cells. ..
  36. Oppedisano F, Pochini L, Galluccio M, Indiveri C. The glutamine/amino acid transporter (ASCT2) reconstituted in liposomes: electrical nature of the glutamine/glutamate antiport. Ital J Biochem. 2007;56:275-8 pubmed
    ..The membrane potential did not affect the glutamine/glutamine antiport whereas it stimulated about two fold the glutamine/glutamate antiport rate. ..
  37. Gliddon C, Shao Z, LeMaistre J, Anderson C. Cellular distribution of the neutral amino acid transporter subtype ASCT2 in mouse brain. J Neurochem. 2009;108:372-83 pubmed publisher
    ..These results suggest that ASCT2 may be an important neuronal neutral amino acid transporter and highlight a discrepancy between findings of astrocyte ASCT2 function in tissue culture and brain in situ. ..
  38. Huang Q, Li N, Zhu W, Li Q, Li J. Glutamine transporter ASCT2 was down-regulated in ischemic injured human intestinal epithelial cells and reversed by epidermal growth factor. JPEN J Parenter Enteral Nutr. 2007;31:86-93 pubmed
    ..These findings may help in the choice of the nutrition support manner and clinical therapy of ischemia-damaged intestinal epithelial cells. ..
  39. Ochiai H, Higa K, Hishiyama N, Hisamatsu S, Fujise H. Characterization of several amino acid transports and glutamine metabolism in MOLT4 human T4 leukemia cells. Clin Lab Haematol. 2006;28:399-404 pubmed
    ..Based on these results, the high glutamate concentration in MOLT4 was speculated to be synthesized from transported glutamine by active glutaminase. ..
  40. Dun Y, Mysona B, Itagaki S, Martin Studdard A, Ganapathy V, Smith S. Functional and molecular analysis of D-serine transport in retinal Müller cells. Exp Eye Res. 2007;84:191-9 pubmed
  41. Lucas M, Seidel N, Porada C, Quigley J, Anderson S, Malech H, et al. Improved transduction of human sheep repopulating cells by retrovirus vectors pseudotyped with feline leukemia virus type C or RD114 envelopes. Blood. 2005;106:51-8 pubmed
  42. Wieland H, Ullrich S, Lang F, Neumeister B. Intracellular multiplication of Legionella pneumophila depends on host cell amino acid transporter SLC1A5. Mol Microbiol. 2005;55:1528-37 pubmed
    ..pneumophila without compromising viability of host cells. These observations suggest that replication of L. pneumophila depends on the function of host cell SLC1A5. ..
  43. Ma C, Stinson J, Zhang Y, Abbott J, Weinreich M, Hauk P, et al. Germline hypomorphic CARD11 mutations in severe atopic disease. Nat Genet. 2017;49:1192-1201 pubmed publisher
    ..Our findings indicate that a single hypomorphic mutation in CARD11 can cause potentially correctable cellular defects that lead to atopic dermatitis. ..
  44. Pinto V, Amaral J, Silva E, Simão S, Cabral J, Afonso J, et al. Age-related changes in the renal dopaminergic system and expression of renal amino acid transporters in WKY and SHR rats. Mech Ageing Dev. 2011;132:298-304 pubmed publisher
    ..This activation may be the consequence of a counter-regulatory mechanism for stimuli leading to sodium reabsorption. ..
  45. Kles K, Tappenden K. Hypoxia differentially regulates nutrient transport in rat jejunum regardless of luminal nutrient present. Am J Physiol Gastrointest Liver Physiol. 2002;283:G1336-42 pubmed
    ..Additional information regarding the mechanisms regulating nutrient transport in the hypoperfused intestine is critical for optimizing the composition of enteral nutrient formulas. ..
  46. Dolinska M, Dybel A, Zabłocka B, Albrecht J. Glutamine transport in C6 glioma cells shows ASCT2 system characteristics. Neurochem Int. 2003;43:501-7 pubmed
  47. Hassanein M, Hight M, Buck J, Tantawy M, Nickels M, Hoeksema M, et al. Preclinical Evaluation of 4-[18F]Fluoroglutamine PET to Assess ASCT2 Expression in Lung Cancer. Mol Imaging Biol. 2016;18:18-23 pubmed publisher
    ..Given the potential of ASCT2 as a lung cancer biomarker, this and other tracers reflecting ASCT2 levels could emerge as precision imaging diagnostics in this setting. ..
  48. Ohtsuki S. [Physiological function of blood-brain barrier transporters as the CNS supporting and protecting system]. Yakugaku Zasshi. 2004;124:791-802 pubmed
  49. Zander C, Albers T, Grewer C. Voltage-dependent processes in the electroneutral amino acid exchanger ASCT2. J Gen Physiol. 2013;141:659-72 pubmed publisher
    ..Despite some differences, transport mechanism and interaction with Na(+) appear to be highly conserved between ASCT2 and the other members of the solute carrier 1 family, which transport acidic amino acids. ..
  50. Uchiyama T, Matsuda Y, Wada M, Takahashi S, Fujita T. Functional regulation of Na+-dependent neutral amino acid transporter ASCT2 by S-nitrosothiols and nitric oxide in Caco-2 cells. FEBS Lett. 2005;579:2499-506 pubmed
    ..These results suggested that functional up-regulation of ASCT2 by SNAP might be partially associated with an increase in the density of transporter protein via de novo synthesis. ..
  51. Sidoryk M, Obara M, Albrecht J. Selective decrease of SN1(SNAT3) mRNA expression in human and rat glioma cells adapted to grow in acidic medium. Neurochem Int. 2006;48:547-52 pubmed
    ..AI did not affect the total Gln uptake, and only slightly decreased the system N-mediated component of the uptake. Hence, SN1(SNAT3) does not seem to be involved in the adaptation of cultured glioma cells to acidic millieu. ..
  52. Henneberger C, Bard L, King C, Jennings A, Rusakov D. NMDA receptor activation: two targets for two co-agonists. Neurochem Res. 2013;38:1156-62 pubmed publisher
    ..Here we discuss how the spatial distribution of co-agonist sources and uptake mechanisms, together with diffusional properties of the synaptic environment, could shape NMDAR co-agonist supply and therefore NMDAR-dependent plasticity. ..
  53. Pinho M, Pinto V, Serrão M, Jose P, Soares da Silva P. Underexpression of the Na+-dependent neutral amino acid transporter ASCT2 in the spontaneously hypertensive rat kidney. Am J Physiol Regul Integr Comp Physiol. 2007;293:R538-47 pubmed
    ..The activity and expression of the ASCT2 transporter were considerably lower in the SHR cells. ..