Sodium Iodide Symporter (NIS) and Thyroid

Abstract

2 idase (TPO) and incorporation into tyrosyl residues along the thyroglobulin (Tg) backbone. The thyroid hormones T3 and T4 are synthesized by coupling of two iodotyro-sine residues and stored in the colloid. All of these steps are stimulated by pituitary-derived thyroid stimulating hormone (TSH), which interacts with the TSH receptor at the basolateral membrane of thyroidal cells, through the cAMP pathway (Figure 1) 1 . In addition to its key role in thyroid physiology, NIS and NIS-mediated iodide accumulation in the thyroid gland represent crucial prerequisites for diagnostic scin-tigraphic imaging as well as for the highly efficient radi-oiodine therapy of benign and malignant thyroid diseas-es. Cloning of the NIS gene in 1996 by N. Carrasco's group 2 represented a major breakthrough in the study of thyroidal iodide transport, and allowed investigation of NIS-related thyroid disorders, including autoimmune thyroid disease and NIS gene mutations, as well as pos-sible therapeutic applications of NIS, which will be sum-marized in the present article. Molecular characterization and regulation of NIS Cloning and sequencing of the rat sodium iodide sym-porter (rNIS) from a Fisher rat thyroid line (FRTL-5)-derived cDNA library 2 revealed a protein of 618 amino acids which is highly homologous (87% identity) to the subsequently cloned human sodium iodide symporter (hNIS) 3 . The human NIS gene is localized on chromo-some 19p12-13.2 and encodes a glycoprotein of 643 ami-no acids with a molecular mass of approximately 70-90 kDa. The coding region of hNIS contains 15 exons inter-rupted by 14 introns and codes for a 3.9 kb mRNA 9 . As a member of the sodium-dependent transporter family, NIS represents an intrinsic membrane protein with 13