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甲状腺碘转运体的克隆与特性分析

Cloning and characterization of the thyroid iodide transporter.

作者信息

Dai G, Levy O, Carrasco N

机构信息

Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

出版信息

Nature. 1996 Feb 1;379(6564):458-60. doi: 10.1038/379458a0.

Abstract

Iodide (I-) is an essential constituent of the thyroid hormones T3 and T4, and is accumulated by the thyroid. The transport of iodide, the first step in thyroid hormogenesis, is catalysed by the Na+/I- symporter, an intrinsic membrane protein that is crucial for the evaluation, diagnosis and treatment of thyroid disorders. Although several other important thyroid proteins involved in hormogenesis have been characterized, the Na+/I- symporter has not. Here we report the isolation of a complementary DNA clone that encodes this symporter, as a result of functional screening of a cDNA library from a rat thyroid-derived cell line (FRTL-5) in Xenopus laevis oocytes. Oocyte microinjection of an RNA transcript made in vitro from this cDNA clone elicited a more than 700-fold increase in perchlorate-sensitive Na+/I- symport activity over background. To our knowledge, this is the first iodide-transporting molecule to have its cDNA cloned, providing a missing link in the thyroid hormone biosynthetic pathway.

摘要

碘离子(I-)是甲状腺激素T3和T4的必需成分,由甲状腺摄取。碘离子转运是甲状腺激素生成的第一步,由钠/碘同向转运体催化,该转运体是一种内在膜蛋白,对甲状腺疾病的评估、诊断和治疗至关重要。尽管已经鉴定了其他几种参与激素生成的重要甲状腺蛋白,但钠/碘同向转运体尚未被鉴定。在此,我们报告了通过对来自大鼠甲状腺衍生细胞系(FRTL-5)的cDNA文库在非洲爪蟾卵母细胞中进行功能筛选,分离出一个编码该同向转运体的互补DNA克隆。将从该cDNA克隆体外转录的RNA转录本显微注射到卵母细胞中,引发了对氯酸盐敏感的钠/碘同向转运活性比背景水平增加了700多倍。据我们所知,这是第一个其cDNA被克隆的碘离子转运分子,填补了甲状腺激素生物合成途径中的一个缺失环节。

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