title: Human pendrin expressed in Xenopus laevis oocytes mediates chloride/formate exchange.
abstract: 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 (36)Cl uptake in X. laevis oocytes. In addition, the uptake of [(14)C]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 [(14)C]formate and formate stimulated the efflux of (36)Cl 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.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Veterans Affairs Medical Center, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Scott
authors.forename: L P
authors.initials: LP
authors.lastname: Karniski
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000235:genetics*; D002712:Chlorides / Q000493:pharmacokinetics*; D005561:Formates / Q000493:pharmacokinetics*; D005731:Ganglionic Stimulants / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D005942:Gluconates / Q000494:pharmacology; D006042:Goiter / Q000235:genetics / Q000378:metabolism; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins; D009865:Oocytes / Q000502:physiology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D000076988:Sulfate Transporters; D014982:Xenopus laevis
chemical_list: D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D002712:Chlorides; D005561:Formates; D005731:Ganglionic Stimulants; D005942:Gluconates; D026901:Membrane Transport Proteins; D000644:Quaternary Ammonium Compounds; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; C030544:formic acid; C027917:tetramethylammonium