The Pendred syndrome gene encodes a chloride-iodide transport protein

Pendred syndrome is the most common form of syndromic deafness and characterized by congenital sensorineural hearing loss and goitre1,2,3. This disorder was mapped to chromosome 7 and the gene causing Pendred syndrome (PDS) was subsequently identified by positional cloning4,5,6. PDS encodes a putative transmembrane protein designated pendrin. Pendrin is closely related to a family of sulfate transport proteins that includes the rat sulfate-anion transporter7 (encoded by Sat-1; 29% amino acid sequence identity), the human diastrophic dysplasia sulfate transporter8 (encoded by DTD; 32%) and the human sulfate transporter 'downregulated in adenoma'9,10 (encoded by DRA; 45%). On the basis of this homology and the presence of a slightly modified sulfate-transporter signature sequence comprising its putative second transmembrane domain6,7,8,9, pendrin has been proposed to function as a sulfate transporter. We were unable to detect evidence of sulfate transport following the expression of pendrin in Xenopus laevis oocytes by microinjection of PDS cRNA or in Sf9 cells following infection with PDS-recombinant baculovirus. The rates of transport for iodide and chloride were significantly increased following the expression of pendrin in both cell systems. Our results demonstrate that pendrin functions as a transporter of chloride and iodide, but not sulfate, and may provide insight into thyroid physiology and the pathophysiology of Pendred syndrome.