Abstract
The Na+/I− symporter (NIS) catalyzes the accumulation of iodide into thyroid cells, an essential step in the biosynthesis of thyroid hormones. As a result of the isolation of the rat NIS cDNA, steadfast advances in the study of NIS at the molecular level have resulted in the following accomplishments: generation of high-affinity anti-NIS antibodies, elucidation of NIS stoichiometry and specificity by electrophysiological analysis, biochemical and immunological experimental testing of the proposed NIS secondary structure model, monitoring the regulation of NIS protein expression by thyroid stimulating hormone and iodide, characterization of the rat NIS gene promoter, isolation of the cDNA clone encoding human NIS and subsequent determination of human NIS genomic organization, description of NIS mutations in patients with congenital lack of iodide transport, and the molecular identification of NIS in extrathyroidal tissues.
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REFERENCES
Abbott, A., and Barker, S. (1996). “Chernobyl damage ‘underestimated.'” Nature 380, 658.
Balter, M. (1995). “Chernobyl's thyroid cancer toll,” Science 270, 1758-1759.
Brooke, J. (1997). “In Idaho, anger over 1950's nuclear tests,” The New York Times, August 13, 1997.
Carrasco, N. (1993). “Iodide transport in the thyroid gland,” Biochim. Biophys. Acta 1154, 65-82.
Cheng, S. H., Gregory, R. J., Marshall, J., Sucharita, P., Souza, D. W., White, G. A., O'Riordan, C. R., and Smith, A. (1990). “Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis,” Cell 63, 827-834.
Dai, G., Levy, O., and Carrasco, N. (1996a). “Cloning and characterization of the thyroid iodide transporter,” Nature 379, 458-460.
Dai, G., Levy, O., Amzel, L. M., and Carrasco, N. (1996b). “The mediator of thyroidal iodide accumulation: the sodium/iodide symporter,” In Handbook of Biological Physics, Vol. II, Transport Processes in Eukaryotic and Prokaryotic Organisms (Konings, W. N., Kaback, H. R., and Lolkema, J. S., eds.), Elsevier, Amsterdam, pp. 343-367.
DeGroot, L. J. (1995). In Endocrinology (DeGroot, I. J., ed.), Grune & Stratton Inc. Orlando, Florida.
Endo, T., Kaneshige, M., Nakazato, M., Ohmori, M., Harii, N., and Onaya, T. (1997). “Thyroid transcription factor-1 activates the promoter activity of rat thyroid Na+/I− symporter gene,” Mol. Endocrinol. 11, 1747-1755.
Eskandari, S., Loo, D. D. F., Dai, G., Levy, O., Wright, E. W., and Carrasco, N. (1997). “Thyroid Na+/I− symporter: mechanism, stoichiometry, and specificity,” J. Biol. Chem. 272, 27230-27238.
Fujiwara, H., Tatsumi, K., Miki, K., Harada, T., Miyai, K., Takai, S., and Amino, N. (1997). “Congenital hypothyroidism caused by a mutation in the Na+/I− symporter,” Nature Genet. 16, 124-125.
Halmi, N. S. (1961). “Thyroidal iodide transport,” Vitam. Horm. 19, 133-163.
Kaminsky, S. M., Levy, O., Salvador, C., Dai, G., and Carrasco, N. (1994). “Na+/I− symport activity is present in membrane vesicles from TSH-deprived non-I− transporting cultured thyroid cells,” Proc. Natl. Acad. Sci. USA 91, 3789-3793.
Kogai, T., Endo, T., Saito, T., Miyazaki, A., Kawaguchi, A., and Onaya, T. (1997). “Regulation by thyroid stimulating hormone of sodium/iodide symporter gene expression and protein levels in FRTL-5 cells,” Endocrinology 138, 2227-2232.
Leger, F. A., Doumith, R., Courpotin, C., Helal, O. B., Davous, N., Aurengo, A. and Savoie, J. C. (1987). “Complete iodide trapping defect in two cases with congenital hypothyroidism: adaptation of thyroid to huge iodide supplementation,” Eur. J. Clin. Invest. 17, 249-255.
Levy, O., and Carrasco, N. (1997). “Structure and function of the thyroid iodide transporter and its implications for thyroid disease,” Curr. Opin. Endocrinol. Diab. 4, 364-370.
Levy, O., Dai, G., Riedel, C., Ginter, C. S., Paul, E. M., Lebowitz, A. N., and Carrasco, N. (1997a). “Characterization of the thyroid Na+/I− symporter with an anti-COOH terminus antibody,” Proc. Natl. Acad. Sci. USA 94, 5568-5573.
Levy, O., Ginter, C. S., De la Vieja, A., Dai, G., Riedel, C., and Carrasco, N. (1997b). “N-linked glycosylation of the thyroid Na+/I− symporter (NIS),” Thyroid 7, 43.
Levy, O., Ginter, C. S., De la Vieja, A., Levy, D., and Carrasco, N. (1998). Identification of a structural requirement for thyroid Na+/I− symporter (NIS) function from analysis of a mutation that causes human congenital hypothyroidism. FEBS Letters (in press).
Likhtarev, I. A., Sobolev, B. G., Kairo, I. A., Tronko, N. D., Bogdanova, T. I., Oleinic, V. A., Epshtein, E. V., and Beral, V. (1995). “Thyroid cancer in the Ukraine,” Nature 375, 365.
Marine, D., and Feiss, H. O. (1915). “The absorption of potassium iodide by perfused thyroid glands and some of the factors modifying it,” J. Pharmacol. Exp. Ther. 7, 557-576.
Martin, G. M., Turk, E., Lostao, M. P., Kerner, C., and Wright, E. M. (1996). “Defects in Na+/glucose cotransporter (SGLT1) trafficking and function caused glucose galactose malabsorption,” Nature Genet. 12, 216-220.
Matsuda, A., and Kosugi, S. (1997). “A homozygous missense mutation of the sodium/iodide symporter gene causing iodide transport defect,” J. Clin. Endocrinol. Metab. 82, 3966-3971.
Ohno, M., Zannini, M., Dai, G., Levy, O., Carrasco, N., and DiLauro, R. (1997). “Transcriptional regulation of the rat Na+/I− symporter gene,” Thyroid 7, 224.
Pohlenz, J., Medeiros-Neto, G., Gross, J. L., Silveiro, S. P., Knobel, M., and Refetoff, S. (1997). “Hypothyroidism in a Brazilian kindred due to iodide trapping defect caused by a homozygous mutation in the sodium/iodide symporter gene,” Biochem. Biophys. Res. Commun. 240, 488-491.
Paire, A., Bernier-Valentin F., Selmi-Ruby, S., and Rousset, B. (1997). “Characterization of the rat thyroid iodide transporter using anti-peptide antibodies,” J. Biol. Chem. 272, 18245-18249.
Smanik, P. A., Liu, Q., Furminger, T. L., Ryu, K-Y., Xing, S., Mazzaferri, E. L., and Jhiang, S. M. (1996). “Cloning of the human sodium iodide symporter,” Biochem. Biophys. Res. Commun. 226, 339-345.
Smanik, P. A., Ryu, K., Thiel, K. S., Mazzaferri, E. L., and Jhiang, S. M. (1997). “Expression, exon-intron organization, and chromosome mapping of the human sodium iodide symporter,” Endocrinology 138, 3555-3558.
Stubbe, P., Schulte, F. J., and Heidemann, P. (1986). “Iodine deficiency and brain development,” Bibl. Nutr. Dieta 38, 206-208.
Tong, Q., Ryu, K-Y., and Jhiang, S. M. (1997). “Promoter characterization of the rat Na+/I− symporter gene,” Biochem. Biophys. Res. Commun. 239, 34-41.
Turk, E., Kerner, C. J., Lostao M. P., and Wright, E. M. (1996). “Membrane topology of the human Na+/glucose cotransporter SGLT1,” J. Biol. Chem. 271, 1925-1934.
Uyttersprot, N., Pelgrims, N., Carrasco, N., Gervy, C., Maenhaut, C., Dumont, J. E., and Miot, F. (1997). “Moderate doses of iodide in vivo inhibit cell proliferation and the expression of thyroid peroxidase and the Na+/I− symporter mRNAs in dog thyroid,” Mol. Cell. Endocrinol. 131, 195-203.
Vilijn, F., and Carrasco, N. (1989). “Expression of the thyroid sodium/iodide symporter in Xenopus laevis oocytes,” J. Biol. Chem. 264, 11901-11903.
Wald M. L. (1997). “Thousands have thyroid cancer from atomic test,” The New York Times, August 2, 1997.
Werner, S. C., and Ingbar, S. (1991). In The Thyroid: A Fundamental and Clinical Text (Braverman, L. E., and Utiger, R. D., eds), J. B. Lippincott, Philadelphia, pp. 1-1362.
Wolff, J. (1964). “Transport of iodide and other anions in the thyroid gland,” Physiol. Rev. 44, 45-90.
Wolff, J. (1969). “Iodide goiter and the pharmacologic effects of excess iodide,” Am. J. Med. 47, 101-124.
Wolff, J. (1983). “Congenital goitre with defective iodide transport,” Endocrinol. Rev. 4, 250-254.
Yoshida, A., Sasaki, N., Mori, A., Taniguchi, S., Mitani, Y., Ueta, Y., Hattori, K., Sato, R., Hisatome, I., Mori, T., Shigemasa, C., and Kosugi, S. (1997). “Different electrophysiological character of I−, ClO −4 , and SCN− in the transport by Na+/I− symporter,” Biochem. Biophys. Res. Commun. 231, 731-734.