Molecular analysis of the sodium/iodide symporter: Impact on thyroid and extrathyroid pathophysiology

The Na+/I- symporter (NIS) is an intrinsic membrane protein that mediates t he active transport of iodide into the thyroid and other tissues, such as s alivary glands, gastric mucosa, and lactating mammary gland. NIS plays key roles in thyroid pathophysiology as the route by which iodide reaches the g land for thyroid hormone biosynthesis and as a means for diagnostic scintig raphic imaging and for radioiodide therapy in hyperthyroidism and thyroid c ancer. The molecular characterization of NIS started with the 1996 isolatio n of a cDNA encoding rat NIS and has since continued at a rapid pace. Anti- NIS antibodies have been prepared and used to study NIS topology and its se condary structure. The biogenesis and posttranslational modifications of NI S have been examined, a thorough electrophysiological analysis of NIS has b een conducted, the cDNA encoding human NIS (hNIS) has been isolated, the ge nomic organization of hNIS has been elucidated, the regulation of NIS by th yrotropin and I- has been analyzed, the regulation of NIS transcript:ion ha s been studied, spontaneous NIS mutations have been identified as causes of congenital iodide transport defect resulting in hypothyroidism, the roles of NIS in thyroid cancer and thyroid autoimmune disease have been examined, and the expression and regulation of NIS in extrathyroidal tissues have be en investigated. In gene therapy experiments, the rat NIS gene has been tra nsduced into various types of human cells, which then exhibited active iodi de transport and became susceptible to destruction with radioiodide. The co ntinued molecular analysis of NIS clearly holds the potential of an even gr eater impact on a wide spectrum of fields, ranging from structure/function of transport proteins to the diagnosis and treatment of cancer, both in the thyroid and beyond.