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Gene Review

SLC1A4  -  solute carrier family 1 (glutamate/neutral...

Homo sapiens

Synonyms: ASCT-1, ASCT1, Alanine/serine/cysteine/threonine transporter 1, Neutral amino acid transporter A, SATT, ...
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Disease relevance of SLC1A4


Psychiatry related information on SLC1A4

  • CONCLUSIONS: Music therapy is a noninvasive and inexpensive intervention that appears to reduce mood disturbance in patients undergoing HDT/ASCT [4].
  • 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 [5].

High impact information on SLC1A4

  • In the non-HIV setting, patients with relapsed Hodgkin disease (HD) or non-Hodgkin lymphoma (NHL) have a better chance of long-term remission with high-dose chemotherapy with autologous stem cell rescue (ASCT) compared with conventional salvage chemotherapy [6].
  • These results suggest that high-dose therapy and ASCT during first remission may improve the survival and prognosis of patients with poor-risk intermediate- and high-grade lymphoma [3].
  • Intensification included one cycle of high-dose cytarabine (HDAC) followed by etoposide/cyclophosphamide and mitoxantrone/diaziquone (group I), three HDAC cycles (group II), four intermediate-dose cytarabine (IDAC) or HDAC cycles (group III), or one HDAC/etoposide cycle and autologous stem-cell transplantation (ASCT; group IV) [7].
  • Patients 60 years or younger with progressive lymphoma were eligible to receive HDCT with ASCT [8].
  • A great improvement was found in the ASCT group (P<.01 for emotional and role function, fatigue, appetite, and constipation), whereas no significant changes were observed for the SCT group [9].

Chemical compound and disease context of SLC1A4


Biological context of SLC1A4


Anatomical context of SLC1A4

  • SATT expression in HeLa cells did not induce the transport of radiolabeled L-cysteine, L-glutamate, or related dicarboxylates [15].
  • Northern blot hybridization revealed high levels of SATT mRNA in human skeletal muscle, pancreas, and brain, intermediate levels in heart, and low levels in liver, placenta, lung, and kidney [15].
  • SATT may represent one of multiple activities that exhibit System ASC-like transport characteristics in diverse tissues and cell lines [15].
  • In contrast to Gln uptake, Thr uptake was more active in cells cultured in the absence of Gln and showed neither pH dependence nor lithium tolerance in either medium, which is typical of an uptake mediated by the widespread ASCT1 isoform of system ASC [18].
  • In contrast, the profile for rat astrocytes was a mixture of that for HEK293 cells expressing rat ASCT1 and that for the cells expressing rat ASCT2 [19].

Associations of SLC1A4 with chemical compounds

  • Expression of SATT cDNA in HeLa cells induced stereospecific uptake of L-serine, L-alanine, and L-threonine that was not inhibited by excess (3 mM) 2-(methylamino)-isobutyric acid, a specific substrate for the System A amino acid transporter [15].
  • Screening for cDNAs encoding proteins similar to the sodium-coupled glutamate transporter GLAST1 led to the isolation of a cDNA clone coding for a protein that turned out to be identical to the recently described neutral amino acid transporter ASCT1 [14].
  • 5. However, lowering the assay pH to 5.5 significantly enhanced the interaction of the ASCT1 carrier with anionic amino acids such as cysteate, in a pH-dependent manner [16].
  • ASCT-1 is a neutral amino acid exchanger with chloride channel activity [20].
  • ASCT1 was conditioned with CBV + mitoxantrone (30 mg/m2) and ASCT2 (cytarabine 6 g/m2 melphalan 140 mg/m2 and total body irradiation at 12 Gy or busulfan 16 (n = 4) than 12 mg/kg) [2].

Other interactions of SLC1A4

  • ASCT1 immunoreactivity was cytoplasmic, whereas Glut1 was membranous [1].
  • RESULTS: Hematologic recovery was normal after ASCT1 but delayed platelet recovery was observed after ASCT2 with busulfan in the conditioning regimen [2].
  • ASCT1 is a member of the glutamate transporter superfamily cloned from human brain and characterized as a Na(+)-dependent neutral amino-acid exchanger, which displays substrate-induced chloride-channel activity and mediates concentrative transport of alanine [21].

Analytical, diagnostic and therapeutic context of SLC1A4


  1. Expression of the neutral amino acids transporter ASCT1 in esophageal carcinomas. Younes, M., Pathak, M., Finnie, D., Sifers, R.N., Liu, Y., Schwartz, M.R. Anticancer Res. (2000) [Pubmed]
  2. Feasibility of tandem autologous stem-cell transplantation (ASCT) in induction failure or very unfavorable (UF) relapse from Hodgkin's disease (HD). SFGM/GELA Study Group. Brice, P., Divine, M., Simon, D., Coiffier, B., Leblond, V., Simon, M., Voilat, L., Devidas, A., Morschhauser, F., Rohrlich, P., André, M., Lepage, E., Ferme, C. Ann. Oncol. (1999) [Pubmed]
  3. Results of high-dose therapy and autologous bone marrow/stem cell transplantation during remission in poor-risk intermediate- and high-grade lymphoma: international index high and high-intermediate risk group. Nademanee, A., Molina, A., O'Donnell, M.R., Dagis, A., Snyder, D.S., Parker, P., Stein, A., Smith, E., Planás, I., Kashyap, A., Spielberger, R., Fung, H., Wong, K.K., Somlo, G., Margolin, K., Chow, W., Sniecinski, I., Vora, N., Blume, K.G., Niland, J., Forman, S.J. Blood (1997) [Pubmed]
  4. Music therapy for mood disturbance during hospitalization for autologous stem cell transplantation: a randomized controlled trial. Cassileth, B.R., Vickers, A.J., Magill, L.A. Cancer (2003) [Pubmed]
  5. 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. Weis, S., Llenos, I.C., Dulay, J.R., Verma, N., Sabunciyan, S., Yolken, R.H. Journal of neural transmission (Vienna, Austria : 1996) (2007) [Pubmed]
  6. Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas. Krishnan, A., Molina, A., Zaia, J., Smith, D., Vasquez, D., Kogut, N., Falk, P.M., Rosenthal, J., Alvarnas, J., Forman, S.J. Blood (2005) [Pubmed]
  7. Outcome of induction and postremission therapy in younger adults with acute myeloid leukemia with normal karyotype: a cancer and leukemia group B study. Farag, S.S., Ruppert, A.S., Mrózek, K., Mayer, R.J., Stone, R.M., Carroll, A.J., Powell, B.L., Moore, J.O., Pettenati, M.J., Koduru, P.R., Stamberg, J., Baer, M.R., Block, A.W., Vardiman, J.W., Kolitz, J.E., Schiffer, C.A., Larson, R.A., Bloomfield, C.D. J. Clin. Oncol. (2005) [Pubmed]
  8. Treatment of primary progressive Hodgkin's and aggressive non-Hodgkin's lymphoma: is there a chance for cure? Josting, A., Reiser, M., Rueffer, U., Salzberger, B., Diehl, V., Engert, A. J. Clin. Oncol. (2000) [Pubmed]
  9. Health-related quality of life 1 year after allogeneic or autologous stem-cell transplantation: a prospective study. Hjermstad, M.J., Evensen, S.A., Kvaløy, S.O., Fayers, P.M., Kaasa, S. J. Clin. Oncol. (1999) [Pubmed]
  10. A phase I-II study of rituximab, ifosfamide, mitoxantrone and etoposide (R-IME) for B cell non-Hodgkin's lymphoma prior to and after high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT). Joyce, R.M., Regan, M., Ottaway, J., Umiel, T., Tetreault, J.C., Levine, J., McDermott, D., Hurley, D., Giallombardo, N., Smith, T., Lamontagne, D., Uhl, L., Avigan, D. Ann. Oncol. (2003) [Pubmed]
  11. Patients with multiple myeloma may safely undergo autologous transplantation despite ongoing RSV infection and no ribavirin therapy. Aslan, T., Fassas, A.B., Desikan, R., Siegel, D., Munshi, N., Mehta, J., Singhal, S., Barlogie, B., Anaissie, E. Bone Marrow Transplant. (1999) [Pubmed]
  12. Long-term results of a risk-adapted approach to melphalan conditioning in autologous peripheral blood stem cell transplantation for primary (AL) amyloidosis. Perfetti, V., Siena, S., Palladini, G., Bregni, M., Di Nicola, M., Obici, L., Magni, M., Brunetti, L., Gianni, A.M., Merlini, G. Haematologica (2006) [Pubmed]
  13. Induction with oral chemotherapy (CID) followed by early autologous stem cell transplantation for de novo multiple myeloma patients. Spencer, A., Seldon, M., Deveridge, S., Cobcroft, R., Cull, G., Marlton, P., Enno, A., Gill, D. Hematol. J. (2004) [Pubmed]
  14. Human neutral amino acid transporter ASCT1: structure of the gene (SLC1A4) and localization to chromosome 2p13-p15. Hofmann, K., Düker, M., Fink, T., Lichter, P., Stoffel, W. Genomics (1994) [Pubmed]
  15. Cloning and expression of a novel Na(+)-dependent neutral amino acid transporter structurally related to mammalian Na+/glutamate cotransporters. Shafqat, S., Tamarappoo, B.K., Kilberg, M.S., Puranam, R.S., McNamara, J.O., Guadaño-Ferraz, A., Fremeau, R.T. J. Biol. Chem. (1993) [Pubmed]
  16. Expressed human hippocampal ASCT1 amino acid transporter exhibits a pH-dependent change in substrate specificity. Tamarappoo, B.K., McDonald, K.K., Kilberg, M.S. Biochim. Biophys. Acta (1996) [Pubmed]
  17. Glutamate reduces secretion of l-serine in astrocytes isolated from stroke-prone spontaneously hypertensive rats. Yamagata, K., Shoji, Y., Terashima, T., Yokogoshi, H. Neuroscience (2006) [Pubmed]
  18. Glutamine transport in C6 glioma cells: substrate specificity and modulation in a glutamine deprived culture medium. Dolińska, M., Dybel, A., Hilgier, W., Zielińska, M., Zabłocka, B., Buzańska, L., Albrecht, J. J. Neurosci. Res. (2001) [Pubmed]
  19. Functional identification of ASCT1 neutral amino acid transporter as the predominant system for the uptake of L-serine in rat neurons in primary culture. Yamamoto, T., Nishizaki, I., Nukada, T., Kamegaya, E., Furuya, S., Hirabayashi, Y., Ikeda, K., Hata, H., Kobayashi, H., Sora, I., Yamamoto, H. Neurosci. Res. (2004) [Pubmed]
  20. ASCT-1 is a neutral amino acid exchanger with chloride channel activity. Zerangue, N., Kavanaugh, M.P. J. Biol. Chem. (1996) [Pubmed]
  21. Transport of proline and hydroxyproline by the neutral amino-acid exchanger ASCT1. Pinilla-Tenas, J., Barber, A., Lostao, M.P. J. Membr. Biol. (2003) [Pubmed]
  22. Outcome of rheumatoid arthritis and psoriasis following autologous stem cell transplantation for hematologic malignancy. Cooley, H.M., Snowden, J.A., Grigg, A.P., Wicks, I.P. Arthritis Rheum. (1997) [Pubmed]
  23. High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience. Rodríguez, J., Caballero, M.D., Gutiérrez, A., Marín, J., Lahuerta, J.J., Sureda, A., Carreras, E., León, A., Arranz, R., Fernández de Sevilla, A., Zuazu, J., García-Laraña, J., Rifon, J., Varela, R., Gandarillas, M., SanMiguel, J., Conde, E. Ann. Oncol. (2003) [Pubmed]
  24. Myeloablative radiochemotherapy followed by reinfusion of purged autologous stem cells for Waldenström's macroglobulinaemia. Dreger, P., Glass, B., Kuse, R., Sonnen, R., von Neuhoff, N., Bolouri, H., Kneba, M., Schmitz, N. Br. J. Haematol. (1999) [Pubmed]
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