Human pendrin expressed in Xenopus laevis oocytes mediates chloride/formate exchange
Human pendrin expressed in Xenopus laevis oocytes mediates chloride/formate exchange
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DOI：
10.1152/ajpcell.2000.278.1.c207
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发表时间：
2000-01-01
影响因子：
5.5
通讯作者：
Karniski, LP
中科院分区：
文献类型：
--
作者：
Scott, DA;Karniski, LP
Pendred综合征，以先天性感音神经性听力损失和甲状腺肿大为特征，是综合征性耳聋最常见的形式之一。导致Pendred综合征（PDS）的基因编码一种名为penddrin的蛋白质，这种蛋白质在甲状腺、肾脏和胎儿耳蜗中表达。Pendrin作为一种碘化物和氯化物转运体，但其在听力损失和甲状腺肿发展中的作用尚不清楚。在本研究中，我们研究了pendrin介导的非洲爪蟾卵母细胞阴离子运输的机制。在摄取培养基中加入未标记的甲酸盐，可抑制大鼠卵母细胞对penddrin介导的Cl-36的摄取。此外，与水注射对照相比，注射PDS cRNA的卵母细胞对[C-14]甲酸盐的摄取受到刺激。这些结果表明甲酸盐是潘德林的底物。此外，氯化物刺激[C-14]甲酸的外排，甲酸刺激表达penddrin的卵母细胞中Cl-36的外排，结果与penddrin介导的氯化物/甲酸交换一致。这些数据表明，penddrin在功能上类似于肾氯/甲酸交换剂，它是近端小管中氯运输的重要机制。类似的过程可能参与内耳内离子梯度的发展。
Pendred syndrome, characterized by congenital sensorineural hearing loss and goiter, is one of the most common forms of syndromic deafness. The gene causing Pendred syndrome (PDS) encodes a protein designated pendrin, which is expressed in the thyroid, kidney, and fetal cochlea. Pendrin functions as an iodide and chloride transporter, but its role in the development of hearing loss and goiter is unknown. In this study, we examined the mechanism of pendrin-mediated anion transport in Xenopus laevis oocytes. Unlabeled formate added to the uptake medium inhibited pendrin-mediated Cl-36 uptake in X. laevis oocytes. In addition, the uptake of [C-14]formate was stimulated in oocytes injected with PDS cRNA compared with water-injected controls. These results indicate that formate is a substrate for pendrin. Furthermore, chloride stimulated the efflux of [C-14]formate and formate stimulated the efflux of Cl-36 in oocytes expressing pendrin, results consistent with pendrin-mediated chloride/formate exchange. These data demonstrate that pendrin is functionally similar to the renal chloride/formate exchanger, which serves as an important mechanism of chloride transport in the proximal tubule. A similar process could participate in the development of ion gradients within the inner ear.