Abstract
A cDNA clone highly related to the rat brain taurine transporter has been isolated from a human placental cDNA library. Transfection of this cDNA into HeLa cells results in a marked elevation of taurine transport activity. The activity of the cDNA-induced transporter is dependent on the presence of Na+ as well as Cl-. The Na+/Cl-/taurine stoichiometry for the cloned transporter is 2:1:1. The transporter is specific for taurine and other beta-amino acids, including beta-alanine, and exhibits high affinity for taurine (Michaelis-Menten constant approximately 6 microM). The clone consists of a coding region 1863 bp long (including the termination codon), flanked by a 376 bp-long 5' non-coding region and a 625 bp-long 3' non-coding region. The nucleotide sequence of the coding region predicts a 620-amino acid protein with a calculated M(r) of 69,853. Northern-blot analysis of poly(A)+ RNA from several human tissues indicates a complex expression pattern differing across tissues. The principal transcript, 6.9 kb in size, is expressed abundantly in placenta and skeletal muscle, at intermediate levels in heart, brain, lung, kidney and pancreas and at low levels in liver. Cultured human cell lines derived from placenta (JAR and BeWo), intestine (HT-29), cervix (HeLa) and retinal pigment epithelium (HRPE), which are known to possess Na(+)- and Cl(-)-coupled taurine transport activity, also contain the 6.9 kb transcript. Somatic cell hybrid and in situ hybridization studies indicate that the cloned taurine transporter is localized to human chromosome 3 p24-->p26.
Full text
PDF







Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Amara S. G., Pacholczyk T. Sodium-dependent neurotransmitter reuptake systems. Curr Opin Neurobiol. 1991 Jun;1(1):84–90. doi: 10.1016/0959-4388(91)90014-x. [DOI] [PubMed] [Google Scholar]
- Blakely R. D., Clark J. A., Rudnick G., Amara S. G. Vaccinia-T7 RNA polymerase expression system: evaluation for the expression cloning of plasma membrane transporters. Anal Biochem. 1991 May 1;194(2):302–308. doi: 10.1016/0003-2697(91)90233-j. [DOI] [PubMed] [Google Scholar]
- Brandsch M., Miyamoto Y., Ganapathy V., Leibach F. H. Regulation of taurine transport in human colon carcinoma cell lines (HT-29 and Caco-2) by protein kinase C. Am J Physiol. 1993 May;264(5 Pt 1):G939–G946. doi: 10.1152/ajpgi.1993.264.5.G939. [DOI] [PubMed] [Google Scholar]
- Clark J. A., Amara S. G. Amino acid neurotransmitter transporters: structure, function, and molecular diversity. Bioessays. 1993 May;15(5):323–332. doi: 10.1002/bies.950150506. [DOI] [PubMed] [Google Scholar]
- Cool D. R., Leibach F. H., Bhalla V. K., Mahesh V. B., Ganapathy V. Expression and cyclic AMP-dependent regulation of a high affinity serotonin transporter in the human placental choriocarcinoma cell line (JAR). J Biol Chem. 1991 Aug 25;266(24):15750–15757. [PubMed] [Google Scholar]
- Ghisolfi J. Taurine and the premature. Biol Neonate. 1987;52 (Suppl 1):78–86. doi: 10.1159/000242741. [DOI] [PubMed] [Google Scholar]
- 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]
- HARRIS H., SEARLE A. G. Urinary amino-acids in mice of different genotypes. Ann Eugen. 1953 Feb;17(3):165–167. doi: 10.1111/j.1469-1809.1953.tb02544.x. [DOI] [PubMed] [Google Scholar]
- Harper M. E., Saunders G. F. Localization of single copy DNA sequences of G-banded human chromosomes by in situ hybridization. Chromosoma. 1981;83(3):431–439. doi: 10.1007/BF00327364. [DOI] [PubMed] [Google Scholar]
- Hibbard J. U., Pridjian G., Whitington P. F., Moawad A. H. Taurine transport in the in vitro perfused human placenta. Pediatr Res. 1990 Jan;27(1):80–84. doi: 10.1203/00006450-199001000-00021. [DOI] [PubMed] [Google Scholar]
- Huxtable R. J. Physiological actions of taurine. Physiol Rev. 1992 Jan;72(1):101–163. doi: 10.1152/physrev.1992.72.1.101. [DOI] [PubMed] [Google Scholar]
- Huxtable R. J. Taurine in the central nervous system and the mammalian actions of taurine. Prog Neurobiol. 1989;32(6):471–533. doi: 10.1016/0301-0082(89)90019-1. [DOI] [PubMed] [Google Scholar]
- Jhiang S. M., Fithian L., Smanik P., McGill J., Tong Q., Mazzaferri E. L. Cloning of the human taurine transporter and characterization of taurine uptake in thyroid cells. FEBS Lett. 1993 Mar 1;318(2):139–144. doi: 10.1016/0014-5793(93)80008-i. [DOI] [PubMed] [Google Scholar]
- Karl P. I., Fisher S. E. Taurine transport by microvillous membrane vesicles and the perfused cotyledon of the human placenta. Am J Physiol. 1990 Mar;258(3 Pt 1):C443–C451. doi: 10.1152/ajpcell.1990.258.3.C443. [DOI] [PubMed] [Google Scholar]
- Kennelly P. J., Krebs E. G. Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases. J Biol Chem. 1991 Aug 25;266(24):15555–15558. [PubMed] [Google Scholar]
- Kulanthaivel P., Cool D. R., Ramamoorthy S., Mahesh V. B., Leibach F. H., Ganapathy V. Transport of taurine and its regulation by protein kinase C in the JAR human placental choriocarcinoma cell line. Biochem J. 1991 Jul 1;277(Pt 1):53–58. doi: 10.1042/bj2770053. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kulanthaivel P., Leibach F. H., Mahesh V. B., Ganapathy V. Tyrosine residues are essential for the activity of the human placental taurine transporter. Biochim Biophys Acta. 1989 Oct 16;985(2):139–146. doi: 10.1016/0005-2736(89)90358-1. [DOI] [PubMed] [Google Scholar]
- Kuo S. M., Stipanuk M. H. Changes in cysteine dioxygenase and cysteinesulfinate decarboxylase activities and taurine levels in tissues of pregnant or lactating rat dams and their fetuses or pups. Biol Neonate. 1984;46(5):237–248. doi: 10.1159/000242071. [DOI] [PubMed] [Google Scholar]
- Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
- Leibach J. W., Cool D. R., Del Monte M. A., Ganapathy V., Leibach F. H., Miyamoto Y. Properties of taurine transport in a human retinal pigment epithelial cell line. Curr Eye Res. 1993 Jan;12(1):29–36. doi: 10.3109/02713689308999493. [DOI] [PubMed] [Google Scholar]
- Liu Q. R., López-Corcuera B., Nelson H., Mandiyan S., Nelson N. Cloning and expression of a cDNA encoding the transporter of taurine and beta-alanine in mouse brain. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12145–12149. doi: 10.1073/pnas.89.24.12145. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacDonald R. J., Swift G. H., Przybyla A. E., Chirgwin J. M. Isolation of RNA using guanidinium salts. Methods Enzymol. 1987;152:219–227. doi: 10.1016/0076-6879(87)52023-7. [DOI] [PubMed] [Google Scholar]
- Mandla S., Scriver C. R., Tenenhouse H. S. Decreased transport in renal basolateral membrane vesicles from hypertaurinuric mice. Am J Physiol. 1988 Jul;255(1 Pt 2):F88–F95. doi: 10.1152/ajprenal.1988.255.1.F88. [DOI] [PubMed] [Google Scholar]
- Miyamoto Y., Balkovetz D. F., Leibach F. H., Mahesh V. B., Ganapathy V. Na+ + Cl- -gradient-driven, high-affinity, uphill transport of taurine in human placental brush-border membrane vesicles. FEBS Lett. 1988 Apr 11;231(1):263–267. doi: 10.1016/0014-5793(88)80744-0. [DOI] [PubMed] [Google Scholar]
- Moyer M. S., Insler N., Dumaswala R. The role of chloride in taurine transport across the human placental brush-border membrane. Biochim Biophys Acta. 1992 Aug 10;1109(1):74–80. doi: 10.1016/0005-2736(92)90189-s. [DOI] [PubMed] [Google Scholar]
- 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]
- Ramamoorthy S., Bauman A. L., Moore K. R., Han H., Yang-Feng T., Chang A. S., Ganapathy V., Blakely R. D. Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2542–2546. doi: 10.1073/pnas.90.6.2542. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramamoorthy S., Cool D. R., Mahesh V. B., Leibach F. H., Melikian H. E., Blakely R. D., Ganapathy V. Regulation of the human serotonin transporter. Cholera toxin-induced stimulation of serotonin uptake in human placental choriocarcinoma cells is accompanied by increased serotonin transporter mRNA levels and serotonin transporter-specific ligand binding. J Biol Chem. 1993 Oct 15;268(29):21626–21631. [PubMed] [Google Scholar]
- Ramamoorthy S., Kulanthaivel P., Leibach F. H., Mahesh V. B., Ganapathy V. Solubilization and functional reconstitution of the human placental taurine transporter. Biochim Biophys Acta. 1993 Feb 9;1145(2):250–256. doi: 10.1016/0005-2736(93)90296-c. [DOI] [PubMed] [Google Scholar]
- Ramamoorthy S., Leibach F. H., Mahesh V. B., Ganapathy V. Selective impairment of taurine transport by cyclosporin A in a human placental cell line. Pediatr Res. 1992 Jul;32(1):125–127. doi: 10.1203/00006450-199207000-00024. [DOI] [PubMed] [Google Scholar]
- Rozen R., Scriver C. R., Mohyuddin F. Hypertaurinuria in the C57BL/6J mouse: altered transport at the renal basolateral membrane. Am J Physiol. 1983 Feb;244(2):F150–F155. doi: 10.1152/ajprenal.1983.244.2.F150. [DOI] [PubMed] [Google Scholar]
- Smith K. E., Borden L. A., Wang C. H., Hartig P. R., Branchek T. A., Weinshank R. L. Cloning and expression of a high affinity taurine transporter from rat brain. Mol Pharmacol. 1992 Oct;42(4):563–569. [PubMed] [Google Scholar]
- Sturman J. A. Nutritional taurine and central nervous system development. Ann N Y Acad Sci. 1986;477:196–213. doi: 10.1111/j.1749-6632.1986.tb40337.x. [DOI] [PubMed] [Google Scholar]
- Sturman J. A. Taurine in development. Physiol Rev. 1993 Jan;73(1):119–147. doi: 10.1152/physrev.1993.73.1.119. [DOI] [PubMed] [Google Scholar]
- Tiruppathi C., Brandsch M., Miyamoto Y., Ganapathy V., Leibach F. H. Constitutive expression of the taurine transporter in a human colon carcinoma cell line. Am J Physiol. 1992 Nov;263(5 Pt 1):G625–G631. doi: 10.1152/ajpgi.1992.263.5.G625. [DOI] [PubMed] [Google Scholar]
- Turner R. J. Quantitative studies of cotransport systems: models and vesicles. J Membr Biol. 1983;76(1):1–15. doi: 10.1007/BF01871450. [DOI] [PubMed] [Google Scholar]
- Uchida S., Kwon H. M., Yamauchi A., Preston A. S., Marumo F., Handler J. S. Molecular cloning of the cDNA for an MDCK cell Na(+)- and Cl(-)-dependent taurine transporter that is regulated by hypertonicity. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8230–8234. doi: 10.1073/pnas.89.17.8230. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Uhl G. R., Hartig P. R. Transporter explosion: update on uptake. Trends Pharmacol Sci. 1992 Dec;13(12):421–425. doi: 10.1016/0165-6147(92)90133-q. [DOI] [PubMed] [Google Scholar]
- Yang-Feng T. L., Floyd-Smith G., Nemer M., Drouin J., Francke U. The pronatriodilatin gene is located on the distal short arm of human chromosome 1 and on mouse chromosome 4. Am J Hum Genet. 1985 Nov;37(6):1117–1128. [PMC free article] [PubMed] [Google Scholar]