Structure and function of the thyroid iodide transporter and its implications for thyroid disease

The thyroid iodide (I−) transporter, a Na+/I− symporter (NIS), is an intrinsic 618-amino-acid membrane glycoprotein that catalyzes the accumulation of I− into thyrocytes, an essential step in the biosynthesis of thyroid hormones. Remarkable progress has recently been achieved in the study of NIS at the molecular level as a result of the isolation of the cDNA encoding rat NIS. Among the main accomplishments are the isolation of the cDNA clone encoding human NIS, electrophysiological analysis and elucidation of the mechanism, stoichiometry, and specificity of rat NIS, generation of anti-rat NIS antibodies for use in NIS characterization, proposal and experimental testing of NIS secondary structure models, analysis of the regulation of NIS expression by thyroid-stimulating hormone and I−, characterization of the regulation of the rat NIS gene, elucidation of the genomic organization of human NIS, identification of an NIS mutation in a case of congenital lack of I“ transport, and detection of anti-NIS autoantibodies in thyroid autoimmune disease.