title: The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications.
abstract: Active iodide (I-) transport in both the thyroid and some extrathyroidal tissues is mediated by the Na+/I-symporter (NIS). In the thyroid, NIS-mediated I-uptake plays a pivotal role in thyroid hormone (TH) biosynthesis. THs are key during embryonic and postembryonic development and critical for cell metabolism at all stages of life. The molecular characterization of NIS in 1996 and the use of radioactive I-isotopes have led to significant advances in the diagnosis and treatment of thyroid cancer and provide the molecular basis for studies aimed at extending the use of radioiodide treatment in extrathyroidal malignancies. This review focuses on the most recent findings on I-homeostasis and I-transport deficiency-causing NIS mutations, as well as current knowledge of the structure/function properties of NIS and NIS regulatory mechanisms. We also discuss employing NIS as a reporter gene using viral vectors and stem cells in imaging, diagnostic, and therapeutic procedures.
authors.affiliation: Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut 06510; email: nancy.carrasco@yale.edu.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ravera
authors.affiliation: Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut 06510; email: nancy.carrasco@yale.edu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Reyna-Neyra
authors.affiliation: Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut 06510; email: nancy.carrasco@yale.edu.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ferrandino
authors.affiliation: Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: L Mario
authors.initials: LM
authors.lastname: Amzel
authors.affiliation: Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut 06510; email: nancy.carrasco@yale.edu.
authors.forename: Nancy
authors.initials: N
authors.lastname: Carrasco
mesh_terms: D000818:Animals; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007454:Iodides / Q000378:metabolism*; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000099209:Sodium-Iodide Symporters
chemical_list: D007454:Iodides; D027981:Symporters; D000099209:Sodium-Iodide Symporters
keywords: NIS mutations; gene transfer studies; imaging and radioiodide therapy; sodium/iodide symporter; structure/function; thyroid hormones