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.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Reardon, W. & Tembath, R.C. Pendred syndrome. J. Med. Genet. 33, 1037–1040 (1996).
Reardon, W. et al. Pendred syndrome: 100 years of underascertainment? Q. J. Med. 90, 443–447 ( 1997).
Gorlin, J.R., Toriello, H.V. & Cohen, M.M. Jr Goiter and profound congenital sensorineural hearing loss (Pendred syndrome). in Hereditary Hearing Loss and Its Syndromes 337–339 (Oxford University Press, New York, 1995).
Sheffield, V.C. et al. Pendred syndrome maps to chromosome 7q21-34 and is caused by an intrinsic defect in thyroid iodine organification. Nature Genet. 12, 424–426 ( 1996).
Coyle, B. et al. Pendred syndrome (goitre and sensorineural hearing loss) maps to chromosome 7 in the region containing non-syndromic deafness gene DFNB4. Nature Genet. 12, 421– 423 (1996).
Everett, L.A. et al. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nature Genet. 17, 411–422 (1997).
Bissig, M., Hagenbuch, B., Stieger, B., Koller, T. & Meier, P.J. Functional expression cloning of the canalicular sulfate transport system of rat hepatocytes . J. Biol. Chem. 269, 3017–3021 (1994).
Hastbacka, J. et al. The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping. Cell 78,1073–1087 ( 1994).
Silberg, D.G., Wang, W., Moseley, R.H. & Traber, P.G. The Down regulated in Adenoma (dra) gene product encodes an intestine-specific membrane sulfate transport protein. J. Biol. Chem. 270, 11897 –11902 (1995).
Hoglund, P. et al. Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea. Nature Genet. 14, 316–319 (1996).
Aronson, P.S. The renal proximal tubule: A model for diversity of anion exchangers and stilbene-sensitive anion transporters. Annu. Rev. Physiol. 51, 419–441 (1989).
Karniski, L.P. et al. Immunolocalization of sat-1 sulfate/oxalate/bicarbonate anion exchanger in rat kidney. Am. J. Physiol. 275, F79–F87 (1998).
Carrasco, N. Iodide transport in the thyroid gland. Biochim. Biophys. Acta. 1154, 65–82 ( 1993).
Dai, G., Levy O. & Carrasco, N. Cloning and characterization of the thyroid iodide transporter. Nature 379, 458– 460 (1996).
Karniski, L.P. & Aronson, P.S. Anion exchange pathways for Cl– transport in rabbit renal microvillus membranes. Am. J. Physiol. 253, F513– F521 (1987).
Brown, C.D.A., Dunk, C.R. & Turnberg, L.A. Cl-HCO3 exchange and anion conductance in rat duodenal apical membrane vesicles. Am. J. Physiol. 257, G661–G667 (1989).
Halligan, R.D., Shelat, H. & Kahn, A.M. Na+-independent Cl-HCO3 exchange in sarcolemmal vesicles from vascular smooth muscle. Am. J. Physiol. 260, C347–C354 ( 1991).
Moseley, R.H. et al. Downregulated in adenoma gene encodes a chloride transporter defective in congenital chloride diarrhea. Am. J. Physiol. 276, G185–G192 (1999).
Trotter, W.R. The association of deafness with thyroid dysfunction. Br. Med. Bull. 16, 92–98 ( 1960).
Hagen, G.A. et al. Peroxidase deficiency in familial goiter with iodide organification defect. N. Engl. J. Med. 285, 1394– 1398 (1971).
Abramawicz, M.J. et al. Identification of a mutation in the coding sequence of the human thyroid peroxidase gene causing congenital goiter. J. Clin. Invest. 90, 1200–1204 (1992).
Johnsen T., Jorgensen, M.B. & Johnsen, S. Mondini cochlea in Pendred's syndrome. A histological study. Acta Otolaryngol. 102, 239– 247 (1986).
Li, X.C. et al. A mutation in PDS causes non-syndromic recessive deafness. Nature Genet. 18, 215– 217 (1998).
Liman E.R, Tytgat, J. & Hess, P. Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs. Neuron 9, 861–871 ( 1992).
This work was supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs and NIH grant DK-47881 (L.P.K.), and by NIH grant HG00457 (V.C.S.).
About this article
Novel pendrin inhibitor attenuates airway hyperresponsiveness and mucin expression in experimental murine asthma
Journal of Allergy and Clinical Immunology (2019)
International Journal of Pediatric Otorhinolaryngology (2019)
Seminars in Nephrology (2019)
Communications Biology (2019)
Pendrin Mediates Bicarbonate Secretion and Enhances Cystic Fibrosis Transmembrane Conductance Regulator Function in Airway Surface Epithelia
American Journal of Respiratory Cell and Molecular Biology (2019)