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钠/碘同向转运体:其分子特征的最新进展

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

作者信息

Darrouzet Elisabeth, Lindenthal Sabine, Marcellin Didier, Pellequer Jean-Luc, Pourcher Thierry

机构信息

SBTN, bât 170, centre de Marcoule, BP 17171, 30207 Bagnols sur Cèze CEDEX, France; Laboratoire TIRO, Faculté de médecine, Université de Nice Sophia-Antipolis, 28 Avenue de Valombrose, 06107 Nice CEDEX, France; CAL, TIRO, F-06107 Nice, France.

出版信息

Biochim Biophys Acta. 2014 Jan;1838(1 Pt B):244-53. doi: 10.1016/j.bbamem.2013.08.013. Epub 2013 Aug 27.

DOI:10.1016/j.bbamem.2013.08.013
PMID:23988430
Abstract

The sodium/iodide symporter (NIS or SLC5A5) is an intrinsic membrane protein implicated in iodide uptake 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 iodide transporter 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 SSS family, the Vibrio parahaemolyticus sodium/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.

摘要

钠/碘同向转运体(NIS或SLC5A5)是一种内在膜蛋白,参与碘进入甲状腺滤泡细胞的过程。它在碘代谢和甲状腺调节中起着关键作用,其功能在良性和恶性甲状腺疾病的诊断和治疗中得到广泛应用。目前正在大力开展基于NIS的基因治疗研究,该治疗也可用于非甲状腺肿瘤的放射治疗。NIS在其他组织中也有表达,如唾液腺、胃以及哺乳期的乳腺,但其在这些组织中的生理作用尚不清楚。甲状腺碘转运体的分子特性大约在十五年前得以阐明。它属于钠/溶质同向转运体超家族(SSS,也属于人类转运体家族SLC5),在人类中由13个跨膜螺旋和643个氨基酸残基组成。通过利用SSS家族成员之一——副溶血性弧菌钠/半乳糖同向转运体(vSGLT)的高分辨率结构,以及对导致先天性碘转运缺陷(ITD)的基因突变的研究,人们获得了有关NIS结构/功能关系的知识。本综述将总结目前关于NIS分子特征的知识。

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