Department of Molecular and Cellular Physiology (C.P., N.C.), Yale University School of Medicine, New Haven, Connecticut 06510; and Department of Molecular Pharmacology (M.P.-B.), Albert Einstein College of Medicine, Bronx, New York 10469.
Endocr Rev. 2014 Feb;35(1):106-49. doi: 10.1210/er.2012-1036. Epub 2013 Dec 4.
The Na(+)/I(-) symporter (NIS) is the plasma membrane glycoprotein that mediates active I(-) transport in the thyroid and other tissues, such as salivary glands, stomach, lactating breast, and small intestine. In the thyroid, NIS-mediated I(-) uptake plays a key role as the first step in the biosynthesis of the thyroid hormones, of which iodine is an essential constituent. These hormones are crucial for the development of the central nervous system and the lungs in the fetus and the newborn and for intermediary metabolism at all ages. Since the cloning of NIS in 1996, NIS research has become a major field of inquiry, with considerable impact on many basic and translational areas. In this article, we review the most recent findings on NIS, I(-) homeostasis, and related topics and place them in historical context. Among many other issues, we discuss the current outlook on iodide deficiency disorders, the present stage of understanding of the structure/function properties of NIS, information gleaned from the characterization of I(-) transport deficiency-causing NIS mutations, insights derived from the newly reported crystal structures of prokaryotic transporters and 3-dimensional homology modeling, and the novel discovery that NIS transports different substrates with different stoichiometries. A review of NIS regulatory mechanisms is provided, including a newly discovered one involving a K(+) channel that is required for NIS function in the thyroid. We also cover current and potential clinical applications of NIS, such as its central role in the treatment of thyroid cancer, its promising use as a reporter gene in imaging and diagnostic procedures, and the latest studies on NIS gene transfer aimed at extending radioiodide treatment to extrathyroidal cancers, including those involving specially engineered NIS molecules.
钠/碘同向转运体（NIS）是一种位于细胞膜的糖蛋白，介导甲状腺和其他组织（如唾液腺、胃、哺乳期乳腺和小肠）中的碘离子主动转运。在甲状腺中，NIS 介导的碘离子摄取在甲状腺激素的生物合成中起着关键作用，碘是甲状腺激素的必需成分。这些激素对胎儿和新生儿中枢神经系统和肺部的发育以及所有年龄段的中间代谢都至关重要。自 1996 年 NIS 被克隆以来，NIS 的研究已成为一个主要的研究领域，对许多基础和转化领域产生了重大影响。本文综述了 NIS、碘离子稳态及相关主题的最新发现，并将其置于历史背景下。在许多其他问题中，我们讨论了碘缺乏症的现状、对 NIS 结构/功能特性的理解阶段、从碘离子转运缺陷导致 NIS 突变的特征中获得的信息、从新报道的原核转运蛋白晶体结构和 3 维同源建模中获得的见解，以及 NIS 以不同的化学计量转运不同底物的新发现。本文还综述了 NIS 的调节机制，包括涉及甲状腺中 NIS 功能的新发现的钾离子通道。我们还介绍了 NIS 的当前和潜在的临床应用，例如其在甲状腺癌治疗中的核心作用、作为成像和诊断程序中报告基因的有前途的用途，以及最新的 NIS 基因转移研究，旨在将放射性碘治疗扩展到甲状腺外癌，包括涉及专门设计的 NIS 分子的研究。
