Abstract
Members of the solute carrier families (SLC) 32, 36, and 38, together also designated the β-group of SLCs, are known to transport neutral amino acids. In this paper, we show that these three families were present before the split of the animal lineage and that they are likely to share a common decent. We also show that the APF transporters found in plants are most likely homologous to the mammalian β-group, suggesting that this type of transporters arouse early in the evolution of eukaryotes. We performed detailed tissue expression analysis of all the members of the β-group in rat and found several examples of highly specific expression patterns, with SLC38A7 being exclusively found in liver, SLC38A5 in blood, and SLC38A4 in muscle and liver. Moreover, we found that SLC38A10 is expressed in several endocrine organs. We also found that SLC38A1 is highly up regulated in the cortex from rats treated with diazepam and that SLC38A2 is significantly down regulated in the same tissue. 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.
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Altschul, S. F., Madden, T. L., Schaffer, A. A., et al. (1997). Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucleic Acids Research, 25, 3389–3402.
Aubrey, K. R., Rossi, F. M., Ruivo, R., et al. (2007). The transporters GlyT2 and VIAAT cooperate to determine the vesicular glycinergic phenotype. Journal of Neuroscience, 27, 6273–6281.
Boll, M., Daniel, H., & Gasnier, B. (2004). The SLC36 family: proton-coupled transporters for the absorption of selected amino acids from extracellular and intracellular proteolysis. Pflügers Archiv, 447, 776–779.
Boudko, D. Y., Kohn, A. B., Meleshkevitch, E. A., et al. (2005). Ancestry and progeny of nutrient amino acid transporters. Proceedings of the National Academy of Sciences of the United States of America, 102, 1360–1365.
Boulland, J. L., Osen, K. K., Levy, L. M., et al. (2002). Cell-specific expression of the glutamine transporter SN1 suggests differences in dependence on the glutamine cycle. European Journal of Neurology, 15, 1615–1631.
Boulland, J. L., Rafiki, A., Levy, L. M., Storm-Mathisen, J., & Chaudhry, F. A. (2003). Highly differential expression of SN1, a bidirectional glutamine transporter, in astroglia and endothelium in the developing rat brain. Glia, 41, 260–275.
Chaudhry, F. A., Reimer, R. J., Krizaj, D., et al. (1999). Molecular analysis of system N suggests novel physiological roles in nitrogen metabolism and synaptic transmission. Cell, 99, 769–780.
Conti, F., & Melone, M. (2006). The glutamine commute: lost in the tube? Neurochemistry International, 48, 459–464.
Daniels, R. W., Collins, C. A., Gelfand, M. V., et al. (2004). Increased expression of the Drosophila vesicular glutamate transporter leads to excess glutamate release and a compensatory decrease in quantal content. Journal of Neuroscience, 24, 10466–10474.
Desforges, M., Lacey, H. A., Glazier, J. D., et al. (2006). SNAT4 isoform of system A amino acid transporter is expressed in human placenta. American Journal of Physiology, Cell Physiology, 290, C305–C312.
Eddy, S. R. (1998). Profile hidden Markov models. Bioinformatics, 14, 755–763.
Felsenstein, J. (1998). Phylogenies from molecular sequences—Inference and reliability. Annual Review of Genetics, 22, 521–565.
Fredriksson, R., Lagerstrom, M. C., Lundin, L. G., & Schioth, H. B. (2003). The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Molecular Pharmacology, 63, 1256–1272.
Gasnier, B. (2004). The SLC32 transporter, a key protein for the synaptic release of inhibitory amino acids. Pflügers Archiv, 447, 756–759.
Gonzalez-Gonzalez, I. M., Cubelos, B., Gimenez, C., & Zafra, F. (2005). Immunohistochemical localization of the amino acid transporter SNAT2 in the rat brain. Neuroscience, 130, 61–73.
Gu, S., Villegas, C. J., & Jiang, J. X. (2005). Differential regulation of amino acid transporter SNAT3 by insulin in hepatocytes. Journal of Biological Chemistry, 280, 26055–26062.
Haitina, T., Lindblom, J., Renstrom, T., & Fredriksson, R. (2006). Fourteen novel human members of mitochondrial solute carrier family 25 (SLC25) widely expressed in the central nervous system. Genomics, 88, 779–790.
Hatanaka, T., Huang, W., Ling, R., et al. (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. Biochimica et Biophysica acta, 1510, 10–17.
Hediger, M. A., Romero, M. F., Peng, J. B., et al. (2004). The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteinsIntroduction. Pflügers Archiv, 447, 465–468.
Jacobsson, J. A., Haitina, T., Lindblom, J., & Fredriksson, R. (2007). Identification of six putative human transporters with structural similarity to the drug transporter SLC22 family. Genomics, 90, 595–609.
Lagerstrom, M. C., Hellstrom, A. R., Gloriam, D. E., et al. (2006). The G protein-coupled receptor subset of the chicken genome. PLoS Computers in Biology, 2, e54.
Lander, E. S., Linton, L. M., Birren, B., et al. (2001). Initial sequencing and analysis of the human genome. Nature, 409, 860–921.
Lindblom, J., Johansson, A., Holmgren, A., et al. (2006). Increased mRNA levels of tyrosine hydroxylase and dopamine transporter in the VTA of male rats after chronic food restriction. European Journal of Neuroscience, 23, 180–186.
Mackenzie, B., & Erickson, J. D. (2004). Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family. Pflügers Archiv, 447, 784–795.
Mackenzie, B., Schafer, M. K., Erickson, J. D., et al. (2003). Functional properties and cellular distribution of the system A glutamine transporter SNAT1 support specialized roles in central neurons. Journal of Biological Chemistry, 278, 23720–23730.
Meleshkevitch, E. A., Assis-Nascimento, P., Popova, L. B., et al. (2006). Molecular characterization of the first aromatic nutrient transporter from the sodium neurotransmitter symporter family. The Journal of Experimental Biology, 209, 3183–3198.
Nakanishi, T., Kekuda, R., Fei, Y. J., et al. (2001). Cloning and functional characterization of a new subtype of the amino acid transport system N. American Journal of Physiology, Cell Physiology, 281, C1757–C1768.
Page, R. D. (1996). TreeView: An application to display phylogenetic trees on personal computers. Computer Applications in the Biosciences, 12, 357–358.
Paxinos, G., & Franklin, K. B. J. (2001). The mouse brain in stereotaxic coordinates (2nd ed.). San Diego: Academic.
Paxinos, G., & Watson, C. (1997). The rat brain in stereotaxic coordinates (3rd ed.). San Diego: Academic.
Ramakers, C., Ruijter, J. M., Deprez, R. H., & Moorman, A. F. (2003). Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neuroscience Letters, 339, 62–66.
Romero-Calderon, R., Shome, R. M., Simon, A. F., et al. (2007). A screen for neurotransmitter transporters expressed in the visual system of Drosophila melanogaster identifies three novel genes. Developmental Neurobiology, 67, 550–569.
Su, Y. H., Frommer, W. B., & Ludewig, U. (2004). Molecular and functional characterization of a family of amino acid transporters from Arabidopsis. Plant Physiology, 136, 3104–3113.
Sugawara, M., Nakanishi, T., Fei, Y. J., et al. (2000). Structure and function of ATA3, a new subtype of amino acid transport system A, primarily expressed in the liver and skeletal muscle. Biochimica et Biophysica Acta, 1509, 7–13.
Thompson, J. D., Higgins, D. G., & Gibson, T. J. (1994). Clustal W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Research, 22, 4673–4680.
Vandesompele, J., De Preter, K., Pattyn, F., et al. (2002). Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biology, 3, RESEARCH0034.
Varoqui, H., & Erickson, J. D. (2002). Selective up-regulation of system a transporter mRNA in diabetic liver. Biochemical and Biophysical Research Communications, 290, 903–908.
Venter, J. C., Adams, M. D., Myers, E. W., et al. (2001). The sequence of the human genome. Science, 291, 1304–1351.
Wang, Z., Lo, H. S., Yang, H., et al. (2003). Computational analysis and experimental validation of tumor-associated alternative RNA splicing in human cancer. Cancer Research, 63, 655–657.
Yao, D., Mackenzie, B., Ming, H., et al. (2000). A novel system A isoform mediating Na+/neutral amino acid cotransport. Journal of Biological Chemistry, 275, 22790–22797.
Acknowledgment
We would like to thank Dr. Helgi B. Schiöth for the valuable discussion during the course of the project. We would also like to thank Maria Hägglund for help with in situ hybridizations and Linnea Holmén for the preparation of Supplementary Fig. 1. R.F. was supported by the Swedish Brain Foundation (Hjärnfonden). E.R. was supported by the Swedish Brain Foundation (Hjärnfonden). The studies were supported by AFA, Svenska Läkaresällskapet, Lars Hiertas Foundation, O.E. och Edla Johanssons Foundation, Swedish Royal Academy of Sciences, Längmanska Kulturfonden, the Magnus Bergvall Foundation, and Åhlens Foundation.
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Supplementary data file 1
Primer sequences used for the quantitative real-time PCR (DOC 27 kb)
Supplementary data file 2
Amino acid sequences of the sequences used for the phylogenetic tree in Fig. 2 (DOC 78 kb)
Supplementary Figure 1
Schematic description of the Bregma coordinates for the matrix-dissected sections I–VII used in the rat tissue panel (GIF 28 kb)
Supplementary Figure 2
Amino acid sequence alignment of the known human SLC32, SLC36, and SLC38 members made using MEGAlign from the Lasergene package (DNASTAR). The N- and C-termini were removed, as well as two long insertions in SLC38A4 and SLC38A9, indicated by dots. Gray boxes mark motifs that are 75% conserved, and black lines mark previously described TM regions (Boll et al. 2004; Mackenzie and Erickson 2004). White boxes mark regions conserved between the three families in the β-group (GIF 469 kb)
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Sundberg, B.E., Wååg, E., Jacobsson, J.A. et al. The Evolutionary History and Tissue Mapping of Amino Acid Transporters Belonging to Solute Carrier Families SLC32, SLC36, and SLC38. J Mol Neurosci 35, 179–193 (2008). https://doi.org/10.1007/s12031-008-9046-x
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DOI: https://doi.org/10.1007/s12031-008-9046-x