Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter
Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter
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DOI：
10.1210/me.2001-0309
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发表时间：
2002-10-01
影响因子：
--
通讯作者：
Meier, PJ
中科院分区：
文献类型：
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作者：
Pizzagalli, F;Hagenbuch, B;Meier, PJ
各种两亲性有机化合物的转运是由有机阴离子转运多肽(人的OATP，啮齿动物的OATP)介导的，属于溶质载体家族21A(SLC21A/SLC21a)。其中一些转运蛋白表现出广泛和重叠的底物特异性，并在各种不同的组织中表达。我们分离到了OATP家族的新成员OATP-F(SLC21A14)，并对其进行了功能鉴定。该基因全长3059bp，开放阅读框2136bp，编码712个氨基酸的蛋白质。其基因由15个外显子组成，位于染色体12p12上。OATP-F与OATP-A、OATP-C和OATP8具有47-48%的氨基酸同源性，这些基因聚集在染色体12p12上。OATP-F主要表达于多个脑区和睾丸间质细胞。OATP-F介导T-4和反向T-3的高亲和力转运，表观K-m值分别约为90 nm和128 nm。不太容易被OATP-F转运的底物包括T-3、溴磺化邻苯二甲酸、雌酮-3-硫酸酯和雌二醇-17β-葡萄糖醛酸脂。此外，L-T-4和D-T-4可顺式抑制OATP-F介导的T-4转运，但3，5-二碘甲腺原氨酸不能抑制T-4的转运，表明T4转运不是立体特异性的，但3‘，5’-碘标记对OATP-F的高效转运是重要的。因此，与大多数其他家族成员相比，OATP-F具有更具选择性的底物偏好，并可能在大脑和睾丸中甲状腺激素的分配中发挥重要作用。
Transport of various amphipathic organic compounds is mediated by organic anion transporting polypeptides (OATPs in humans, Oatps in rodents), which belong to the solute carrier family 21A (SLC21A/Slc21a). Several of these transporters exhibit a broad and overlapping substrate specificity and are expressed in a variety of different tissues. We have isolated and functionally characterized OATP-F (SLC21A14), a novel member of the OATP family. The cDNA (3059 bp) contains an open reading frame of 2136 bp encoding a protein of 712 amino acids. Its gene containing 15 exons is located on chromosome 12p12. OATP-F exhibits 47-48% amino acid identity with OATP-A, OATP-C, and OATP8, the genes of which are clustered on chromosome 12p12. OATP-F is predominantly ex-pressed in multiple brain regions and Leydig cells of the testis. OATP-F mediates high affinity transport of T-4 and reverse T-3 with apparent K-m values of approximately 90 nm and 128 nm, respectively. Substrates less well transported by OATP-F include T-3, bromosulfophthalein, estrone-3-sulfate, and estradiol-17beta-glucuronide. Furthermore, OATP-F-mediated T-4 uptake could be cis-inhibited by L-T-4 and D-T-4 but not by 3,5-diiodothyronine, indicating that T4 transport is not stereospecific, but that 3',5'-iodination is important for efficient transport by OATP-F. Thus, in contrast to most other family members, OATP-F has a more selective substrate preference and may play an important role in the disposition of thyroid hormones in brain and testis.