Update on the thyroid sodium iodide symporter: a novel thyroid antigen emerging on the horizon

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Abstract
The ability to transport and concentrate iodide, a fundamental property of normally functioning thyroid epithelial cells, represents a key step in the production of the iodine-containing thyroid hormones. Iodide uptake across the basolateral membrane of thyroid follicular cells is made possible by the Na˛/Iπ symporter (NIS), an active co-transport mechanism that is driven by an inwardly directed Na˛ gradient. In addition to providing a mechanism for several diagnostically useful tests such as the thyroidal radioiodine uptake test and the perchlorate discharge test, NIS-mediated active Iπ- accumulation by thyroid tissue is a crucial requirement for the success of radioactive iodine therapy. As highlighted earlier (1), cloning of the rat NIS from an FRTL-5 cell-derived cDNA library by Carrasco's group has revealed an open reading frame of 1854 nucleotides that encodes a 618 amino acid intrinsic membrane protein with 12 putative membrane-span- ning domains. This discovery has set the stage for Smanik et al. (2), who subsequently cloned the human homologue of NIS from a human thyroid cDNA library. An open reading frame (nucleotides 348-2276) of human NIS (hNIS) encodes a protein of 643 amino acids that shares 84% amino acid identity with recombinant NIS (rNIS) and has a predicted molecular mass of 68·7 kDa. Assignment of the 12 transmem- brane domains in hNIS has been based on the proposed transmembrane domains of the rNIS, in which the two protein sequences are highly conserved. Transient transfection of COS-7 cells with the hNIS cDNA clone resulted in perchlorate-sensitive iodide uptake, confirm- ing expression of functionally intact hNIS. Using reverse transcriptase-polymerase chain reaction, the authors detected hNIS expression at variable levels in papillary thyroid carcinoma tissues, but not in any of the thyroid carcinoma cell lines that lack iodide uptake activity, suggesting that loss of iodide-concentrating activity in thyroid carcinomas may be due to a loss of hNIS expression. Shortly after cloning of hNIS, Kosugi et al. (3) succeeded in establishing stable expression of recombi- nant rNIS in a Chinese hamster ovary (CHO) cell line. Subsequent analysis of its basic biochemical and electrophysiological properties, including time course, Na˛-dependency, kinetics and competitive inhibition by perchlorate and thiocynate, revealed characteristics

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