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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Jul 15;89(14):6639–6643. doi: 10.1073/pnas.89.14.6639

A family of genes encoding neurotransmitter transporters.

Q R Liu 1, S Mandiyan 1, H Nelson 1, N Nelson 1
PMCID: PMC49557  PMID: 1631167

Abstract

The genomic and cDNA clones of the mouse gamma-aminobutyric acid transporter were sequenced and analyzed. The genomic clone contains 12 introns including 1 intron prior to the initiator methionine. The second intron comes immediately after the stretch of amino acids that is most conserved among the neurotransmitter transporters sequenced so far. By using a probe constructed according to this conserved region, several partial genomic clones were isolated. Sequence analysis of those clones reveals not only homology to the family of neurotransmitter transporters within the reading frame but also an identical location of an exon-intron junction after the conserved region. A search of the GenBank data base (April 1991) revealed that two invertebrate genes exhibit homology to the conserved sequence of the above family. One, a Drosophila melanogaster gene, encoded the N-terminal part of a protein homologous to neurotransmitter transporters and the second was in Caenorhabditis elegans. The Drosophila gene contains an intron that starts at a position identical to the corresponding positions of all the mammalian genes of the family.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benian G. M., Kiff J. E., Neckelmann N., Moerman D. G., Waterston R. H. Sequence of an unusually large protein implicated in regulation of myosin activity in C. elegans. Nature. 1989 Nov 2;342(6245):45–50. doi: 10.1038/342045a0. [DOI] [PubMed] [Google Scholar]
  2. Berman S. A., Bursztajn S., Bowen B., Gilbert W. Localization of an acetylcholine receptor intron to the nuclear membrane. Science. 1990 Jan 12;247(4939):212–214. doi: 10.1126/science.1688472. [DOI] [PubMed] [Google Scholar]
  3. Birnbaum M. J., Haspel H. C., Rosen O. M. Cloning and characterization of a cDNA encoding the rat brain glucose-transporter protein. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5784–5788. doi: 10.1073/pnas.83.16.5784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blakely R. D., Berson H. E., Fremeau R. T., Jr, Caron M. G., Peek M. M., Prince H. K., Bradley C. C. Cloning and expression of a functional serotonin transporter from rat brain. Nature. 1991 Nov 7;354(6348):66–70. doi: 10.1038/354066a0. [DOI] [PubMed] [Google Scholar]
  5. Breathnach R., Benoist C., O'Hare K., Gannon F., Chambon P. Ovalbumin gene: evidence for a leader sequence in mRNA and DNA sequences at the exon-intron boundaries. Proc Natl Acad Sci U S A. 1978 Oct;75(10):4853–4857. doi: 10.1073/pnas.75.10.4853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dorit R. L., Schoenbach L., Gilbert W. How big is the universe of exons? Science. 1990 Dec 7;250(4986):1377–1382. doi: 10.1126/science.2255907. [DOI] [PubMed] [Google Scholar]
  7. Guastella J., Nelson N., Nelson H., Czyzyk L., Keynan S., Miedel M. C., Davidson N., Lester H. A., Kanner B. I. Cloning and expression of a rat brain GABA transporter. Science. 1990 Sep 14;249(4974):1303–1306. doi: 10.1126/science.1975955. [DOI] [PubMed] [Google Scholar]
  8. Hall J. D. Modeling functional sites in DNA polymerases. Trends Genet. 1988 Feb;4(2):42–46. doi: 10.1016/0168-9525(88)90065-0. [DOI] [PubMed] [Google Scholar]
  9. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  10. Hoffman B. J., Mezey E., Brownstein M. J. Cloning of a serotonin transporter affected by antidepressants. Science. 1991 Oct 25;254(5031):579–580. doi: 10.1126/science.1948036. [DOI] [PubMed] [Google Scholar]
  11. Horn A. S. Dopamine uptake: a review of progress in the last decade. Prog Neurobiol. 1990;34(5):387–400. doi: 10.1016/0301-0082(90)90033-d. [DOI] [PubMed] [Google Scholar]
  12. Iversen L. L., Kelly J. S. Uptake and metabolism of gamma-aminobutyric acid by neurones and glial cells. Biochem Pharmacol. 1975 May 1;24(9):933–938. doi: 10.1016/0006-2952(75)90422-0. [DOI] [PubMed] [Google Scholar]
  13. James D. E., Strube M., Mueckler M. Molecular cloning and characterization of an insulin-regulatable glucose transporter. Nature. 1989 Mar 2;338(6210):83–87. doi: 10.1038/338083a0. [DOI] [PubMed] [Google Scholar]
  14. Kanner B. I. Ion-coupled neurotransmitter transport. Curr Opin Cell Biol. 1989 Aug;1(4):735–738. doi: 10.1016/0955-0674(89)90042-2. [DOI] [PubMed] [Google Scholar]
  15. Kanner B. I., Schuldiner S. Mechanism of transport and storage of neurotransmitters. CRC Crit Rev Biochem. 1987;22(1):1–38. doi: 10.3109/10409238709082546. [DOI] [PubMed] [Google Scholar]
  16. Kilty J. E., Lorang D., Amara S. G. Cloning and expression of a cocaine-sensitive rat dopamine transporter. Science. 1991 Oct 25;254(5031):578–579. doi: 10.1126/science.1948035. [DOI] [PubMed] [Google Scholar]
  17. Larson R. G., Henning D., Haidar M. A., Jhiang S., Lin W. L., Zhang W. W., Busch H. Genomic structure of the human proliferating cell nucleolar protein P120. Cancer Commun. 1990;2(2):63–71. doi: 10.3727/095535490820874704. [DOI] [PubMed] [Google Scholar]
  18. Maeda M., Oshiman K., Tamura S., Futai M. Human gastric (H+ + K+)-ATPase gene. Similarity to (Na+ + K+)-ATPase genes in exon/intron organization but difference in control region. J Biol Chem. 1990 Jun 5;265(16):9027–9032. [PubMed] [Google Scholar]
  19. Mayser W., Betz H., Schloss P. Isolation of cDNAs encoding a novel member of the neurotransmitter transporter gene family. FEBS Lett. 1991 Dec 16;295(1-3):203–206. doi: 10.1016/0014-5793(91)81418-8. [DOI] [PubMed] [Google Scholar]
  20. Mueckler M., Caruso C., Baldwin S. A., Panico M., Blench I., Morris H. R., Allard W. J., Lienhard G. E., Lodish H. F. Sequence and structure of a human glucose transporter. Science. 1985 Sep 6;229(4717):941–945. doi: 10.1126/science.3839598. [DOI] [PubMed] [Google Scholar]
  21. Nelson H., Mandiyan S., Nelson N. Cloning of the human brain GABA transporter. FEBS Lett. 1990 Aug 20;269(1):181–184. doi: 10.1016/0014-5793(90)81149-i. [DOI] [PubMed] [Google Scholar]
  22. Pacholczyk T., Blakely R. D., Amara S. G. Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter. Nature. 1991 Mar 28;350(6316):350–354. doi: 10.1038/350350a0. [DOI] [PubMed] [Google Scholar]
  23. Padgett R. A., Grabowski P. J., Konarska M. M., Seiler S., Sharp P. A. Splicing of messenger RNA precursors. Annu Rev Biochem. 1986;55:1119–1150. doi: 10.1146/annurev.bi.55.070186.005351. [DOI] [PubMed] [Google Scholar]
  24. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schousboe A., Hjeds H., Engler J., Krogsgaard-Larsen P., Wood J. D. Tissue distribution, metabolism, anticonvulsant efficacy and effect on brain amino acid levels of the glia-selective gamma-aminobutyric acid transport inhibitor 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol in mice and chicks. J Neurochem. 1986 Sep;47(3):758–763. doi: 10.1111/j.1471-4159.1986.tb00676.x. [DOI] [PubMed] [Google Scholar]
  26. Shimada S., Kitayama S., Lin C. L., Patel A., Nanthakumar E., Gregor P., Kuhar M., Uhl G. Cloning and expression of a cocaine-sensitive dopamine transporter complementary DNA. Science. 1991 Oct 25;254(5031):576–578. doi: 10.1126/science.1948034. [DOI] [PubMed] [Google Scholar]
  27. Snyder S. H. Putative neurotransmitters in the brain: selective neuronal uptake, subcellular localization, and interactions with centrally acting drugs. Biol Psychiatry. 1970 Oct;2(4):367–389. [PubMed] [Google Scholar]
  28. Suter B., Kubli E. tRNA(Tyr) genes of Drosophila melanogaster: expression of single-copy genes studied by S1 mapping. Mol Cell Biol. 1988 Aug;8(8):3322–3331. doi: 10.1128/mcb.8.8.3322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tate S. S., Yan N., Udenfriend S. Expression cloning of a Na(+)-independent neutral amino acid transporter from rat kidney. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):1–5. doi: 10.1073/pnas.89.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Teichberg V. I. Glial glutamate receptors: likely actors in brain signaling. FASEB J. 1991 Dec;5(15):3086–3091. doi: 10.1096/fasebj.5.15.1660422. [DOI] [PubMed] [Google Scholar]
  31. Usdin T. B., Mezey E., Chen C., Brownstein M. J., Hoffman B. J. Cloning of the cocaine-sensitive bovine dopamine transporter. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11168–11171. doi: 10.1073/pnas.88.24.11168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yamauchi A., Uchida S., Kwon H. M., Preston A. S., Robey R. B., Garcia-Perez A., Burg M. B., Handler J. S. Cloning of a Na(+)- and Cl(-)-dependent betaine transporter that is regulated by hypertonicity. J Biol Chem. 1992 Jan 5;267(1):649–652. [PubMed] [Google Scholar]
  33. Zucker R. S., Landò L. Mechanism of transmitter release: voltage hypothesis and calcium hypothesis. Science. 1986 Feb 7;231(4738):574–579. doi: 10.1126/science.2868525. [DOI] [PubMed] [Google Scholar]

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