ACELL January 47/1

Scott, Daryl A., and Lawrence P. Karniski. Human pendrin expressed in Xenopus laevis oocytes mediates chloride/ formate exchange. Am. J. Physiol. Cell Physiol. 278: C207– C211, 2000.—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 36Cl uptake in X. laevis oocytes. In addition, the uptake of [14C]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 [14C]formate and formate stimulated the efflux of 36Cl in oocytes expressing pendrin, results consistent with pendrinmediated 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.