Glutamine transporters in mammalian cells and their functions in physiology and cancer

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1863, Issue 10, 2016, Pages 2531-2539

  Bhutia, Yangzom D ^a   Ganapathy, Vadivel ^a  

^a TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER SCHOOL OF MEDICINE   (United States)

Author keywords

Biological function; Cancer; Glutamine transporters; Knockout mouse; Mode of transport; Plasma membrane

Indexed keywords

ANTINEOPLASTIC AGENT; GLUTAMATE TRANSPORTER; SLC1A5 PROTEIN; SLC38A1 PROTEIN; SLC38A2 PROTEIN; SLC38A3 PROTEIN; SLC38A5 PROTEIN; SLC38A7 PROTEIN; SLC38A8 PROTEIN; SLC6A14 PROTEIN; SLC6A19 PROTEIN; SLC7A5 PROTEIN; SLC7A6 PROTEIN; SLC7A7 PROTEIN; SLC7A8 PROTEIN; SLC7A9 PROTEIN; UNCLASSIFIED DRUG; CARRIER PROTEIN; GLUTAMINE; GLUTAMINE TRANSPORT PROTEINS; TUMOR PROTEIN;

BRAIN TISSUE; CANCER THERAPY; CELL MEMBRANE; CELL PROLIFERATION; HUMAN; KIDNEY PARENCHYMA; LIVER; MAMMAL CELL; NEOPLASM; NONHUMAN; PLACENTA TISSUE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REVIEW; ACTIVE TRANSPORT; ANIMAL; ENZYME SPECIFICITY; GENETICS; INBORN ERROR OF METABOLISM; KNOCKOUT MOUSE; MAMMAL; METABOLISM; MOLECULARLY TARGETED THERAPY; MOUSE; MULTIGENE FAMILY; NEOPLASMS; PHYSIOLOGY;

ANIMALS; BIOLOGICAL TRANSPORT, ACTIVE; CARRIER PROTEINS; CELL MEMBRANE; GLUTAMINE; HUMANS; MAMMALS; METABOLISM, INBORN ERRORS; MICE; MICE, KNOCKOUT; MOLECULAR TARGETED THERAPY; MULTIGENE FAMILY; NEOPLASM PROTEINS; NEOPLASMS; SUBSTRATE SPECIFICITY;

EID: 84953298606     PISSN: 01674889     EISSN: 18792596     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2015.12.017     Document Type: Review

References (84)

1. Rennie, M.J., Edwards, R.H.T., Krywawych, S., Davies, C.T.M., Halliday, D., Waterlow, J.C., Millward, D.J., Effect of exercise on protein turnover in man. Clin. Sci. (London) 61 (1981), 627–639.
2. Planche, T., Dzeing, A., Emmerson, A.C., Onanga, M., Kremsner, P.G., Engel, K., Kombila, M., Ngou-Milama, E., Krishna, S., Plasma glutamine and glutamate concentrations in Gabonese children with Plasmodium falciparum infection. Q. J. Med. 95 (2002), 89–97.
3. Newsholme, P., Procopio, J., Lima, M.M., Pithon-Curi, T.C., Curi, R., Glutamine and glutamate—their central role in cell metabolism and function. Cell. Biochem. Funct. 21 (2003), 1–9.
4. Kuhn, K., Schuhmann, K., Stehle, P., Darmaun, D., Furst, P., Determination of glutamine in muscle protein facilitates accurate assessment of proteolysis and de novo synthesis-derived endogenous glutamine production. Am. J. Clin. Nutr. 70 (1999), 484–489.
5. Chang, T.W., Goldberg, A.L., The metabolic fates of amino acids and the formation of glutamine in skeletal muscle. J. Biol. Chem. 252 (1978), 3685–3695.
6. Wise, D.R., Thompson, C.B., Glutamine addiction: a new therapeutic target in cancer. Trends Biochem. Sci. 35 (2010), 427–433.
7. Bhutia, Y.D., Babu, E., Ramachandran, S., Ganapathy, V., Amino acid transporters in cancer and their relevance to “glutamine addiction”: novel targets for the design of a new class of anticancer drugs. Cancer Res. 75 (2015), 1782–1788.
8. Kanai, Y., Clemencon, B., Simonin, A., Leuenberger, M., Lochner, M., Weisstanner, M., Hediger, M.A., The SLC1 high-affinity glutamate and neutral amino acid transporter family. Mol. Aspects Med. 34 (2013), 108–120.
9. Timmerman, L.A., Holton, T., Yuneva, M., Louie, R.J., Pedro, M., Daemen, A., Hu, M., Chan, D.A., Ethier, S.P., van't Veer, L.J., Polyak, K., McCormick, F., Gray, J.W., Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer Cell 24 (2013), 450–465.
10. van Geldermalsen, M., Wang, Q., Nagarajah, R., Marshall, A.D., Thoeng, A., Gao, D., Ritchie, W., Feng, Y., Bailey, C.G., Deng, N., Harvey, K., Beith, J.M., Selinger, C.I., O'Toole, S.A., Rasko, J.E., Holst, J., ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer. Oncogene, 2015 (in press).
11. Huang, F., Zhao, Y., Zhao, J., Wu, S., Jiang, Y., Ma, H., Zhang, T., Upregulated SLC1A5 promotes cell growth and survival in colorectal cancer. Int. J. Clin. Exp. Pathol. 7 (2014), 6006–6014.
12. Hassanein, M., Qian, J., Hoeksema, M.D., Wang, J., Jacobovitz, M., Ji, X., Harris, F.T., Harris, B.K., Boyd, K.L., Chen, H., Eisenberg, R., Massion, P.P., Targeting SLC1A5-mediated glutamine dependence in non-small cell lung cancer. Int. J. Cancer 137 (2015), 1587–1597.
13. Wang, Q., Beaumont, K.A., Otte, N.J., Font, J., Bailey, C.G., van Geldermalsen, M., Sharp, D.M., Tiffen, J.C., Ryan, R.M., Jormakka, M., Haass, N.K., Rasko, J.E., Holst, J., Targeting glutamine transport to suppress melanoma cell growth. Int. J. Cancer 135 (2014), 1060–1071.
14. Ren, P., Yue, M., Xiao, D., Xiu, R., Gan, L., Liu, H., Qing, G., ATF4 and N-Myc coordinate glutamine metabolism in MYCN-amplified neuroblastoma cells through ASCT2 activation. J. Pathol. 235 (2015), 90–100.
15. Wise, D.R., DeBerardinis, R.J., Mancuso, A., Sayed, N., Zhang, X.Y., Pfeiffer, H.K., Nissim, I., Daikin, E., Yudkoff, M., McMahon, S.B., Thompson, C.B., Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc. Natl. Acad. Sci. U.S.A. 105 (2008), 18782–18787.
16. Wang, Q., Hardie, R.A., Hoy, A.J., van Geldermalsen, M., Gao, D., Fazli, L., Sadowski, M.C., Balaban, S., Schreuder, M., Nagarajah, R., Wong, J.J., Metierre, C., Pinello, N., Otte, N.J., Lehman, M.L., Gleave, M., Nelson, C.C., Bailey, C.G., Ritchie, W., Rasko, J.E., Holst, J., Targeting ASCT2-mediated glutamine uptake blocks prostate cancer growth and tumour development. J. Pathol. 236 (2015), 278–289.
17. Reynolds, M.R., Lane, A.N., Robertson, B., Kemp, S., Liu, Y., Hill, B.G., Dean, D.C., Clem, B.F., Control of glutamine metabolism by the tumor suppressor Rb. Oncogene 33 (2014), 556–566.
18. Nicklin, P., Bergman, P., Zhang, B., Triantafellow, E., Wang, H., Nyfeler, B., Yang, H., Hild, M., Kung, C., Wilson, C., Myer, V.E., MacKeigan, J.P., Porter, J.A., Wang, Y.K., Cantley, L.C., Finan, P.M., Murphy, L.O., Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 136 (2009), 521–534.
19. c-cystine/glutamate antiporter: a potential target for therapy of cancer and other diseases. J. Cell. Physiol. 215 (2008), 593–602.
20. 18F-labeled glutamate derivative reveals a dominant pathway in tumor metabolism. Clin. Cancer Res. 17 (2011), 6000–6011.
21. Nakaya, M., Xiao, Y., Zhou, X., Chang, J.H., Chang, M., Cheng, X., Blonska, M., Lin, X., Sun, S.C., Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation. Immunity 40 (2014), 692–705.
22. Yernool, D., Boudker, O., Jin, Y., Gouaux, E., Structure of a glutamate transporter homologue from Pyrococcus horikoshii. Nature 431 (2004), 811–818.
23. Boudker, O., Ryan, R.M., Yernool, D., Shimamot, K., Gouaux, E., Coupling substrate and ion binding to extracellular gate of a sodium-dependent aspartate transporter. Nature 445 (2007), 387–393.
24. Colas, C., Grewer, C., Otte, N.J., Gameiro, A., Albers, T., Singh, K., Shere, H., Bonomi, M., Holst, J., Schlessinger, A., Ligand discovery for the alanine-serine-cysteine transporter (ASCT2, SLC1A5) from homology modeling and virtual screening. PLoS Comput. Biol., 2015 (in press).
25. Rudnick, G., Kramer, R., Blakely, R.D., Murphy, D.L., Verrey, F., The SLC6 transporters: perspectives on structure, functions, regulation, and models for transporter dysfunction. Pflugers Arch. 466 (2014), 25–42.
26. Broer, S., Gether, U., The solute carrier 6 family of transporters. Br. J. Pharmacol. 167 (2012), 256–278.
27. 0,+ as a delivery system for drugs and prodrugs. Curr. Drug Targets Endocr. Metabol. Disord. 5 (2005), 357–364.
28. Bhutia, Y.D., Babu, E., Prasad, P.D., Ganapathy, V., The amino acid transporter SLC6A14 in cancer and its potential use in chemotherapy. Asian J. Pharm. Sci. 9 (2014), 293–303.
29. Sun, L., Rommens, J.M., Corvol, H., Li, W., Li, X., Chiang, T.A., lin, F., Dorfman, R., Busson, P.F., Parekh, R.V., Zelenika, D., Blackman, S.M., Corey, M., Doshi, V.K., Henderson, L., Naughton, K.M., O'Neal, W.K., Pace, R.G., Stonebraker, J.R., Wood, S.D., Wright, F.A., Zielenski, J., Clement, A., Drumm, M.L., Boelle, P.Y., Cutting, G.R., Knowles, M.R., Durie, P.R., Strug, L.J., Multiple apical membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis. Nat. Genet. 44 (2012), 562–569.
30. Corvol, H., Blackman, S.M., Boelle, P.Y., Gallins, P.J., Pace, R.G., Stonebraker, J.R., Accurso, F.J., Clement, A., Collaco, J.M., Dang, H., Dang, A.T., Franca, A., Gong, J., Guillot, L., Keenan, K., Li, W., Lin, F., Patrone, M.V., Raraigh, K.S., Sun, L., Zhou, Y.H., O'Neal, W.K., Sontag, M.K., Levy, H., Durie, P.R., Rommens, J.M., Drumm, M.L., Wright, F.A., Strug, L.J., Cutting, G.R., Knowles, M.R., Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis. Nat. Commun., 6, 2015, 8382.
31. Suviolahti, E., Oksanen, L.J., Ohman, M., Cantor, R.M., Ridderstrale, M., Tuomi, T., Kaprio, J., Rissanen, A., Mustajoki, P., Jousilahti, P., Vartiainen, E., Silander, K., Kilpikari, R., Salomaa, V., Groop, L., Kontula, K., Peltonen, L., Pajukanta, P., The SLC6A14 gene shows evidence of association with obesity. J. Clin. Invest. 112 (2003), 1762–1772.
32. Durand, E., Boutin, P., Meyre, D., Charles, M.A., Clement, K., Dina, C., Froguel, P., Polymorphisms in the amino acid transporter solute carrier family 6 (neurotransmitter transporter) member 14 gene contribute to polygenic obesity in French Caucasians. Diabetes 53 (2004), 2483–2486.
33. Miranda, R.C., Vetter, S.B., Genro, J.P., Campagnolo, P.D., Mattevi, V.S., Vitolo, M.R., Almeida, S., SLC6A14 and 5-HTR2C polymorphisms are associated with food intake and nutritional status in children. Clin. Biochem., 2015 (in press).
34. Flach, C.F., Eriksson, A., Jennische, E., Lange, S., Gunnerek, C., Lonnroth, I., Detection of elafin as a candidate biomarker for ulcerative colitis by whole-genome microarray screening. Inflamm. Bowel Dis. 12 (2006), 837–842.
35. Yanai, H., Ben-Shachar, S., Baram, L., Elad, H., Gitstein, G., Brazowski, E., Tulchinsky, H., Pasmanik-Chor, M., Dotan, I., Gene expression alterations in ulcerative colitis patients after restorative proctocolectomy extend to the small bowel proximal to the pouch. Gut 64 (2015), 756–764.
36. 0,+ (SLC6A14) in colorectal cancer and metastasis in humans. Biochim. Biophys. Acta 1741 (2005), 215–223.
37. 0,+ (SLC6A14) in carcinoma of the cervix. Gynecol. Oncol. 100 (2006), 8–13.
38. 0,+) reveals the potential of the transporter as a drug target for cancer chemotherapy. Biochem. J. 414 (2008), 343–355.
39. Gutierrez, M.L., Corchete, L., Teodosio, C., Sarasquete, M.E., del Mar Abad, M., Iglesias, M., Esteban, C., Sayagues, J.M., Orfao, A., Munoz-Bellvis, L., Identification and characterization of the gene expression profiles for protein coding and non-coding RNAs of pancreatic ductal adenocarcinoma. Oncotarget 6 (2015), 19070–19086.
40. Penheiter, A.R., Erdogan, S., Murphy, S.J., Hart, S.N., Lima, J.F., Rohakhtar, F.R., O'Brien, D.R., Bamlet, W.R., Wuertz, R.E., Smyrk, T.C., Couch, F.J., Vasmatzis, G., Bender, C.E., Carlson, S.K., Transcriptomic and immunohistochemical profiling of SLC6A14 in pancreatic ductal adenocarcinoma. Biomed. Res. Int., 2015, 2015, 593572.
41. 0,+) protein, a highly concentrative and broad specific amino acid transporter, is a novel and effective drug target for treatment of estrogen receptor-positive breast cancer. J. Biol. Chem. 286 (2011), 31830–31838.
42. Babu, E., Bhutia, Y.D., Ramachandran, S., Gnanaparakasam, J.P., Prasad, P.D., Thangaraju, M., Ganapathy, V., Deletion of the amino acid transporter Slc6a14 suppresses tumour growth in spontaneous mouse models of breast cancer. Biochem. J. 469 (2015), 17–23.
43. −-dependent neurotransmitter transporters. Nature 437 (2005), 215–223.
44. Penmatsa, A., Wang, K.H., Gouaux, E., X-Ray structure of dopamine transporter elucidates antidepressant mechanism. Nature 503 (2013), 85–90.
45. 0AT1, cause Hartnup disorder. Nat. Genet. 36 (2004), 999–1002.
46. Seow, H.F., Broer, S., Broer, A., Bailey, C.G., Potter, S.J., Cavanaugh, J.A., Rasko, J.E., Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19. Nat. Genet. 36 (2004), 1003–1007.
47. Singer, D., Camargo, S.M., Collectrin and ACE2 in renal and intestinal amino acid transport. Channels (Austin) 5 (2011), 410–423.
48. 0AT1. Biochem. J. 446 (2012), 135–148.
49. +/neutral amino acid cotransporter (Slc6a19)-deficient mouse. J. Biol. Chem. 286 (2011), 26638–26651.
50. Fotiadis, D., Kanai, Y., Palacin, M., The SLC3 and SLC7 families of amino acid transporters. Mol. Aspects Med. 34 (2013), 139–158.
51. Boado, R.J., Li, J.Y., Nagaya, M., Zhang, C., Pardridge, W.M., Selective expression of the large neutral amino acid transporter at the blood-brain barrier. Proc. Natl. Acad. Sci. U.S.A. 96 (1999), 12079–12084.
52. Matsuo, H., Tsukada, S., Nakata, T., Chairoungdua, A., Kim, D.K., Cha, S.H., Inatomi, J., Yorifuji, H., Fukuda, J., Endou, H., Kanai, Y., Expression of a system L neutral amino acid transporter at the blood-brain barrier. Neuroreport 11 (2000), 3507–3511.
53. Ganapathy, M.E., Leibach, F.H., Mahesh, V.B., Howard, J.C., Devoe, L.D., Ganapathy, V., Characterization of tryptophan transport in human placental brush-border membrane vesicles. Biochem. J. 238 (1986), 201–208.
54. Pochini, L., Scalise, M., Calluccio, M., Indiveri, C., Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health. Front. Chem., 2, 2014, 61.
55. Wang, Q., Holst, J., L-Type amino acid transporter and cancer: targeting the mTORC1 pathway to inhibit neoplasia. Am. J. Cancer Res. 5 (2015), 1281–1294.
56. Ganapathy, V., Thangaraju, M., Prasad, P.D., Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol. Ther. 121 (2009), 29–40.
57. Jewell, J.L., Russell, R.C., Guan, K.L., Amino acid signaling upstream of mTOR. Nat. Rev. Mol. Cell Biol. 14 (2013), 133–139.
58. Taylor, P.M., Role of amino acid transporters in amino acid sensing. Am. J. Clin. Nutr. 99 (2014), 223S–230S (Suppl.).
59. Elorza, A., Soro-Arnaiz, I., Melendez-Rodriguez, F., Rodriguez-Vaello, V., Marsboom, G., de Carcer, G., Acosta-Iborra, B., Albacete-Albacete, L., Ordonez, A., Serrano-Oviedo, L., Gimenez-Bachs, J.M., Vara-Vega, A., Salinas, A., Sanchez-Prieto, R., Martin del Rio, R., Sanchez-Madrid, F., Malumbres, M., Landazuri, M.O., Aragones, J., HIF2α acts as an mTORC1 activator through the amino acid carrier SLC7A5. Mol. Cell 48 (2012), 681–691.
60. Poncet, N., Mitchell, F.E., Ibrahim, A.F., McGuire, V.A., English, G., Arthur, J.S., Shi, Y.B., Taylor, P.M., The catalytic subunit of the system L1 amino acid transporter (slc7a5) facilitates nutrient signaling in mouse skeletal muscle. PLoS One, 9, 2014, e89547.
61. Braun, D., Wirth, E.K., Wohlgemuth, F., Reix, N., Klein, M.O., Gruters, A., Kohrle, J., Schweizer, U., Aminoaciduria, but normal thyroid hormone levels and signaling, in mice lacking the amino acid and thyroid hormone transporter Slc7a8. Biochem. J. 439 (2011), 249–255.
62. Sperandeo, M.P., Andria, G., Sebastio, G., Lysinuric protein intolerance: update and extended mutation analysis of the SLC7A7 gene. Hum. Mutat. 29 (2008), 14–21.
63. Sperandeo, M.P., Annunziata, P., Bozzato, A., Piccolo, P., Maiuri, L., D'Armiento, M., Ballabio, A., Corso, G., Andria, G., Borsani, G., Sebastio, G., Slc7a7 disruption causes fetal growth retardation by downregulating Igf1 in the mouse model of lysinuric protein intolerance. Am. J. Physiol. Cell Physiol. 293 (2007), C191–C198.
64. Chillaron, J., Font-Llitjos, M., Fort, J., Zorzano, A., Goldfarb, D.S., Nunes, V., Palacin, M., Pathophysiology and treatment of cystinuria. Nat. Rev. Nephrol. 6 (2010), 424–434.
65. Feliubadalo, L., Arbones, M.L., Manas, S., Chillaron, J., Visa, J., Rodes, M., Rousaud, F., Zorzano, A., Palacin, M., Nunes, V., Slc7a9-deficient mice develop cystinuria non-I and cystine urolithiasis. Hum. Mol. Genet. 12 (2003), 2097–2108.
66. Mackenzie, B., Erickson, J.D., Sodium-coupled neutral amino acid (system N/A) transporters of the SLC38 gene family. Pflugers Arch. 447 (2004), 784–795.
67. Broer, S., The SLC38 family of sodium-amino acid co-transporters. Pflugers Arch. 466 (2014), 155–172.
68. Wang, H., Huang, W., Sugawara, M., Devoe, L.D., Leibach, F.H., Prasad, P.D., Ganapathy, V., Cloning and functional expression of ATA1, a subtype of amino acid transporter A, from human placenta. Biochem. Biophys. Res. Commun. 273 (2000), 1175–1179.
69. Sugawara, M., Nakanishi, T., Fei, Y.J., Huang, W., Ganapathy, M.E., Leibach, F.H., Ganapathy, V., Cloning of an amino acid transporter with functional characteristics and tissue expression pattern identical to that of system A. J. Biol. Chem. 275 (2000), 16473–16477.
70. Bak, L.K., Schousboe, A., Waagepetersen, H.S., The glutamate-GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. J. Neurochem. 98 (2006), 641–653.
71. Brosnan, M.E., Brosnan, J.T., Hepatic glutamate metabolism: a tale of 2 hepatocytes. Am. J. Clin. Nutr. 90 (2009), 857S–861S.
72. Jenstad, M., Chaudhry, F.A., The amino acid transporters of the glutamate-GABA-glutamine cycle and their impact on insulin and glucagon secretion. Front. Endocrinol. (Lausanne), 4, 2013, 199.
73. Desforges, M., Sibley, C.P., Placental nutrient supply and fetal growth. Int. J. Dev. Biol. 54 (2010), 377–390.
74. Riley, T., Sontag, E., Chen, P., Levine, A., Transcriptional control of human p53-regulated genes. Nat. Rev. Mol. Cell Biol. 9 (2008), 402–412.
75. Jeon, Y.J., Khelifa, S., Ratnikov, B., Scott, D.A., Feng, Y., Parisi, F., Ruller, C., Lau, E., Kim, H., Brill, L.M., Jiang, T., Rimm, D.L., Cardiff, R.D., Mills, G.B., Smith, J.W., Osterman, A.L., Kluger, Y., Ronai, Z.A., Regulation of glutamine carrier proteins by RNF5 determines breast cancer response to ER stress-inducing chemotherapies. Cancer Cell 27 (2015), 354–369.
76. Chaudhry, F.A., Reimer, R.J., Krizaj, D., Barber, D., Storm-Mathisen, J., Copenhagen, D.R., Edwards, R.H., Molecular analysis of system N suggests novel physiological role in nitrogen metabolism and synaptic transmission. Cell 99 (1999), 769–780.
77. +-coupled glutamine transporter. J. Biol. Chem. 275 (2000), 23707–23717.
78. Nakanishi, T., Sugawara, M., Huang, W., Martindale, R.G., Leibach, F.H., Ganapathy, M.E., Prasad, P.D., Ganapathy, V., Structure, function, and tissue distribution pattern of human SN2, a subtype of the amino acid transport system N. Biochem. Biophys. Res. Commun. 281 (2001), 1343–1348.
79. Nakanishi, T., Kekuda, R., Fei, Y.J., Hatanaka, T., Sugawara, M., Martindale, R.G., Leibach, F.H., Prasad, P.D., Ganapathy, V., Cloning and functional characterization of a new subtype of the amino acid transport system N. Am. J. Physiol. Cell Physiol. 281 (2001), C1757–C1768.
80. Umapathy, N.S., Li, W., Mysona, B.A., Smith, S.B., Ganapathy, V., Expression and function of glutamine transporters SN1 (SNAT3) and SN2 (SNAT5) in retinal Muller cells. Invest. Ophthalmol. Vis. Sci. 46 (2005), 3980–3987.
81. Umapathy, N.S., Dun, Y., Martin, P.M./., Duplantier, J.N., Roon, P., Prasad, P.D., Smith, S.B., Ganapathy, V., Expression and function of system N transporters (SN1/SN2 or SNAT3/SNAT5) in retinal ganglion cells. Invest. Ophthalmol. Vis. Sci. 49 (2008), 5151–5160.
82. Hagglund, M.G.A., Sreedharan, S., Nilsson, V.C.O., Shaik, J.H.A., Almkvist, I.M., Backlin, S., Wrange, O., Fredriksson, R., Identification of SLC38A7 (SNAT7) protein as a glutamine transporter expressed in neurons. J. Biol. Chem. 286 (2011), 20500–20511.
83. Hagglund, M.G.A., Hellsten, S.V., Bagchi, S., Philippot, G., Lofqvist, E., Nilsson, V.C.O., Almkvist, I., Karlsson, E., Sreedharan, S., Tafreshiha, A., Fredriksson, R., Transport L-glutamine, L-alanine, L-arginine and L-histidine by the neuron-specific Slc38a8 (SNAT8) in CNS. J. Mol. Biol. 427 (2015), 1495–1512.
84. Chan, K., Busque, S.M., Sailer, M., Stoeger, C., Broer, S., Daniel, H., Rubio-Aliaga, I., Wagner, C.A., Loss of function mutation of the Slc38a3 glutamine transporter reveals its critical role for amino acid metabolism in the liver, brain, and kidney. Pflugers Arch., 2015 (in press).