Originally published In Press as doi:10.1074/jbc.M313648200 on January 8, 2004
J. Biol. Chem., Vol. 279, Issue 13, 13004-13010, March 26, 2004
Functional Characterization of Pendrin in a Polarized Cell System
EVIDENCE FOR PENDRIN-MEDIATED APICAL IODIDE EFFLUX*
Mary P. Gillam
,
Aniket R. Sidhaye,
Eun Jig Lee,
Jonas Rutishauser¶,
Catherine Waeber Stephan||, and
Peter Kopp**
From the
Division of Endocrinology, Metabolism & Molecular Medicine, **Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and ||Endocrine Practice, Fribourg 1700, Switzerland
Pendred's syndrome is an autosomal recessive disorder characterized by sensorineural deafness, goiter, and impaired iodide organification. It is caused by mutations in the PDS/SLC26A4 gene that encodes pendrin. Functionally, pendrin is a transporter of chloride and iodide in Xenopus oocytes and heterologous mammalian cells and a chloride/base exchanger in 
-intercalated cells of the renal cortical collecting duct. The partially impaired thyroidal iodide organification in Pendred's syndrome suggests a possible role of pendrin in iodide transport at the apical membrane of thyroid follicular cells, but experimental evidence for this concept is lacking. The iodide transport properties of pendrin were determined in polarized Madin-Darby canine kidney cells expressing the sodium iodide symporter (NIS), pendrin, or NIS and pendrin using a bicameral system-permitting measurement of iodide content in the basal, intracellular, and apical compartments. Moreover, we determined the functional consequences of two naturally occurring mutations (L676Q and FS306>309X). In polarized Madin-Darby canine kidney cells, NIS mediates uptake at the basolateral membrane. Only minimal amounts of iodide reach the apical compartment in the absence of pendrin. In cells expressing NIS and pendrin, pendrin mediates transport of iodide into the apical chamber. Wild type pendrin also mediates iodide efflux in transiently transfected cells. In contrast, both pendrin mutants lose the ability to promote iodide efflux. These results provide evidence that pendrin mediates apical iodide efflux from polarized mammalian cells loaded with iodide. Consistent with the partial organification defect observed in patients with Pendred's syndrome, naturally occurring mutations of pendrin lead to impaired transport of iodide.
Received for publication, December 12, 2003
* This work was supported by Grant SYN-1199-10 form the Thyroid Research Advisory Council (TRAC) and Grant 1R01DK63024-01 from NIDDK, National Institutes of Health (to P. K.) and a grant from the Endocrine Fellow Foundation (to M. P. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Supported by the Northwestern University Program in Endocrinology, Diabetes and Hormone Action (Grant 2T32 DK07169-22).
¶ Supported by a fellowship from the Kantonale Nachwuchskommission des Kantons (Zürich, Switzerland). Present address: Dept. of Internal Medicine, University of Basel, Basel 4000, Switzerland.
To whom correspondence should be addressed: Division of Endocrinology, Metabolism & Molecular Medicine, Northwestern University, Tarry 15, 303 Chicago Ave., Chicago, IL 60611. Tel.: 312-503-1394; Fax: 312-908-9032; E-mail: p-kopp{at}northwestern.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
H. Frank, N. Groger, M. Diener, C. Becker, T. Braun, and T. Boettger
Lactaturia and Loss of Sodium-dependent Lactate Uptake in the Colon of SLC5A8-deficient Mice
J. Biol. Chem.,
September 5, 2008;
283(36):
24729 - 24737.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J S Yoon, H-J Park, S-Y Yoo, W Namkung, M J Jo, S K Koo, H-Y Park, W-S Lee, K H Kim, and M G Lee
Heterogeneity in the processing defect of SLC26A4 mutants
J. Med. Genet.,
July 1, 2008;
45(7):
411 - 419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Li, K. Richard, B. McKinnon, and R. H. Mortimer
Effect of Iodide on Human Choriogonadotropin, Sodium-Iodide Symporter Expression, and Iodide Uptake in BeWo Choriocarcinoma Cells
J. Clin. Endocrinol. Metab.,
October 1, 2007;
92(10):
4046 - 4051.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Fugazzola, V. Cirello, S. Dossena, S. Rodighiero, M. Muzza, P. Castorina, F. Lalatta, U. Ambrosetti, P. Beck-Peccoz, G. Botta, et al.
High phenotypic intrafamilial variability in patients with Pendred syndrome and a novel duplication in the SLC26A4 gene: clinical characterization and functional studies of the mutated SLC26A4 protein
Eur. J. Endocrinol.,
September 1, 2007;
157(3):
331 - 338.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O Arroyo-Helguera, B Anguiano, G Delgado, and C Aceves
Uptake and antiproliferative effect of molecular iodine in the MCF-7 breast cancer cell line
Endocr. Relat. Cancer,
December 1, 2006;
13(4):
1147 - 1158.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Pfarr, G. Borck, A. Turk, U. Napiontek, A. Keilmann, W. Muller-Forell, P. Kopp, and J. Pohlenz
Goitrous Congenital Hypothyroidism and Hearing Impairment Associated with Mutations in the TPO and SLC26A4/PDS Genes
J. Clin. Endocrinol. Metab.,
July 1, 2006;
91(7):
2678 - 2681.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Tedelind, F. Larsson, C. Johanson, H. C. van Beeren, W. M. Wiersinga, E. Nystrom, and M. Nilsson
Amiodarone Inhibits Thyroidal Iodide Transport in Vitro by a Cyclic Adenosine 5'-Monophosphate- and Iodine-Independent Mechanism
Endocrinology,
June 1, 2006;
147(6):
2936 - 2943.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Suzuki and L. D Kohn
Differential regulation of apical and basal iodide transporters in the thyroid by thyroglobulin.
J. Endocrinol.,
May 1, 2006;
189(2):
247 - 255.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-F. van den Hove, K. Croizet-Berger, F. Jouret, S. E. Guggino, W. B. Guggino, O. Devuyst, and P. J. Courtoy
The Loss of the Chloride Channel, ClC-5, Delays Apical Iodide Efflux and Induces a Euthyroid Goiter in the Mouse Thyroid Gland
Endocrinology,
March 1, 2006;
147(3):
1287 - 1296.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Shepshelovich, L. Goldstein-Magal, A. Globerson, P. M. Yen, P. Rotman-Pikielny, and K. Hirschberg
Protein synthesis inhibitors and the chemical chaperone TMAO reverse endoplasmic reticulum perturbation induced by overexpression of the iodide transporter pendrin
J. Cell Sci.,
April 15, 2005;
118(8):
1577 - 1586.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Quentin, R. Chambrey, M. M. Trinh-Trang-Tan, M. Fysekidis, M. Cambillau, M. Paillard, P. S. Aronson, and D. Eladari
The Cl-/HCO3- exchanger pendrin in the rat kidney is regulated in response to chronic alterations in chloride balance
Am J Physiol Renal Physiol,
December 1, 2004;
287(6):
F1179 - F1188.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Napiontek, G. Borck, W. Muller-Forell, N. Pfarr, A. Bohnert, A. Keilmann, and J. Pohlenz
Intrafamilial Variability of the Deafness and Goiter Phenotype in Pendred Syndrome Caused by a T416P Mutation in the SLC26A4 Gene
J. Clin. Endocrinol. Metab.,
November 1, 2004;
89(11):
5347 - 5351.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Yoshida, I. Hisatome, S. Taniguchi, N. Sasaki, Y. Yamamoto, J. Miake, H. Fukui, H. Shimizu, T. Okamura, T. Okura, et al.
Mechanism of Iodide/Chloride Exchange by Pendrin
Endocrinology,
September 1, 2004;
145(9):
4301 - 4308.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.
