Human pendrin expressed in Xenopus laevis oocytes mediates chloride/formate exchange

Pendred syndrome, characterized by congenital sensorineural hearing loss an d goiter, is one of the most common forms of syndromic deafness. The gene c ausing Pendred syndrome (PDS) encodes a protein designated pendrin, which i s expressed in the thyroid, kidney, and fetal cochlea. Pendrin functions as an iodide and chloride transporter, but its role in the development of hea ring loss and goiter is unknown. In this study, we examined the mechanism o f pendrin-mediated anion transport in Xenopus laevis oocytes. Unlabeled for mate 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. Th ese 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 pend rin-mediated chloride/formate exchange. These data demonstrate that pendrin is functionally similar to the renal chloride/formate exchanger, which ser ves as an important mechanism of chloride transport in the proximal tubule. A similar process could participate in the development of ion gradients wi thin the inner ear.