Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide close to the thyroglobulin iodination site
Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide close to the thyroglobulin iodination site
复制标题
DOI：
10.1096/fj.04-2023fje
复制
发表时间：
2004-08-01
期刊：
影响因子：
4.8
通讯作者：
Dupuy, C
中科院分区：
文献类型：
--
作者：
Gnidehou, S;Caillou, B;Dupuy, C
在甲状腺中，碘酪氨酸脱卤酶作用于甲状腺球蛋白水解过程中释放的单碘酪氨酸和二碘酪氨酸，释放碘化物，然后碘化物可以重新进入激素产生途径。据报道，碘酪氨酸的脱碘主要发生在微粒体中，并由 NADPH 介导。最近，编码具有保守硝基还原酶结构域的蛋白质的两个 cDNA（长度分别为 7401 和 7513 个碱基对）在 GenBank 上发表，分别为碘酪氨酸脱卤酶 1 (DEHAL1) 和碘酪氨酸脱卤酶 1B (DEHAL1B)。我们在此报告我们对其中一种亚型 DEHAL1 的定位和活性的调查。 DEHAL1 mRNA 在甲状腺中高表达，受 cAMP 上调，并编码一种跨膜蛋白，可有效催化 NADPH 依赖性单碘酪氨酸 (L-MIT) 和二碘酪氨酸 (L-DIT) 脱碘，其活性比 L-MIT 更高。碘酪氨酸脱碘酶在 DEHAL1 cDNA 转染的 HEK293 细胞中具有活性，但在 CHO 细胞中没有活性。生物素化实验表明，DEHAL1 蛋白的一部分暴露于细胞表面。免疫组织化学研究表明 DEHAL1 蛋白在甲状腺细胞的顶极积聚。总而言之，这些发现表明脱碘反应发生在甲状腺细胞的顶端，并参与组织部位和/或附近的快速碘化物回收过程。
In the thyroid, iodotyrosine dehalogenase acts on the mono and diiodotyrosines released during the hydrolysis of thyroglobulin to liberate iodide, which can then reenter the hormone-producing pathways. It has been reported that the deiodination of iodotyrosines occurs predominantly in the microsomes and is mediated by NADPH. Recently, two cDNAs, 7401- and 7513-base pairs long that encode proteins with a conserved nitroreductase domain were published in GenBank as iodotyrosine dehalogenase 1 ( DEHAL1) and iodotyrosine dehalogenase 1B (DEHAL1B), respectively. We report here our investigation of the localization and activity of one of these isoforms, DEHAL1. DEHAL1 mRNA is highly expressed in the thyroid, is up-regulated by cAMP, and encodes a transmembrane protein that efficiently catalyzes the NADPH-dependent deiodination of mono (L-MIT) and diiodotyrosine (L-DIT), with greater activity vs. L-MIT. Iodotyrosine deiodinase was active in HEK293 cells transfected by DEHAL1 cDNA, but not in CHO cells. A fraction of DEHAL1 protein is exposed to the cell surface, as indicated by biotinylation experiments. Immunohistochemistry studies showed that DEHAL1 proteins accumulate at the apical pole of thyrocytes. Taken together, these findings indicate that the deiodination reaction occurs at the apical pole of the thyrocyte and is involved in a rapid iodide recycling process at and/or close to the organification site.