The sodium/iodide symporter: State of the art of its molecular characterization

Abstract The sodium/iodide symporter(NIS or SLC5A5) is an intrinsic membrane protein implicated in iodideuptake into thyroid follicular cells. It plays a crucial role in iodine metabolism and thyroid regulation and its function is widely exploited in the diagnosis and treatment of benign and malignant thyroid diseases. A great effort is currently being made to develop a NIS-based gene therapy also allowing the radiotreatment of nonthyroidal tumors. NIS is also expressed in other tissues, such as salivary gland, stomach and mammary gland during lactation, where its physiological role remains unclear. The molecular identity of the thyroid iodidetransporter was elucidated approximately fifteen years ago. It belongs to the superfamily of sodium/solute symporters, SSS(and to the human transporter family, SLC5), and is composed of 13 transmembrane helices and 643 amino acid residues in humans. Knowledge concerning NIS structure/function relationship has been obtained by taking advantage of the high resolution structure of one member of the SSSfamily, the Vibrio parahaemolyticussodium/galactose symporter(vSGLT), and from studies of gene mutations leading to congenital iodine transport defects (ITD). This review will summarize current knowledge regarding the molecular characterization of NIS.