Sulfate Transport Is Not Impaired in Pendred Syndrome Thyrocytes

Kraiem, Zaki; Heinrich, Ronit; Sadeh, O.; Shiloni, Eitan; Nassir, E.; Hazani, Elitsur; Gläser, Benjamin

doi:10.1210/jcem.84.7.5973

Cited by 22 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Initial functional studies of pendrin in Xenopus oocytes and Sf9 insect cells, as well as functional studies using thyrocytes from patients with documented Pendred's syndrome, revealed that pendrin is unable to transport sulfate (21,22). In Xenopus oocytes, pendrin was shown to mediate uptake of chloride and iodide (21) and to act as a chloride/formate exchanger (23).…”

mentioning

confidence: 99%

Functional Characterization of Pendrin in a Polarized Cell System

Gillam

Sidhaye

Lee

et al. 2004

Journal of Biological Chemistry

144

110

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 99%

Functional Characterization of Pendrin in a Polarized Cell System

Gillam

Sidhaye

Lee

et al. 2004

Journal of Biological Chemistry

144

110

View full text Add to dashboard Cite

show abstract

“…Pendrin was first suggested to be a putative sulfate transporter on the basis of strong homologies with a number of known sulfate transporters, although sulfate transport is not impaired in PDS patients' thyroid cells (Kraiem et al 1999). Subsequently, the function of pendrin has been shown to be as a transporter of chloride and iodide (Scott et al 1999).…”

mentioning

confidence: 99%

Expression of Human Pendrin in Diseased Thyroids

Kondo

Nakamura

Suzuki

et al. 2003

J Histochem Cytochem.

View full text Add to dashboard Cite

S U M M A R YWe examined pendrin expression in various diseased thyroid tissues by immunohistochemistry (IHC) using antiserum raised against human pendrin and by real-time quantitative RT-PCR. In normal thyroids the antiserum reacted with the apical membrane of follicular cells and its immunoreactivity was faint. In Graves' thyroids, the IHC expression of pendrin appeared in a pattern similar to that of normal thyroids but it was more extensive and stronger, especially in areas showing marked proliferation of follicular cells. The immunoreactivities of pendrin in nodular goiters varied from case to case. In follicular adenomas, pendrin was localized in the follicle-forming parts of the tumor but was negative in trabecular parts. Pendrin was negative in all follicular carcinomas, papillary carcinomas, and in one case of medullary carcinoma. In quantitive mRNA analysis, the relative values of pendrin mRNA were significantly low in papillary carcinoma ( p Ͻ 0.01), whereas the values in other diseased thyroids were not significantly different from those in normal thyroids. These results suggest that pendrin may play a role in thyroid hormone production as the apical porter of chloride/iodide and investigation of pendrin leads to a better understanding of functional aspects of the iodine transportation system in thyroid diseases.

show abstract

“…Cette déduction n'expliquait pas les anomalies fonctionnelles de l'oreille interne et de la thyroïde dans le syndrome de Pendred. Il a d'ailleurs été rapidement démontré que si la pendrine est effectivement un transporteur ionique, elle ne transporte pas le sulfate mais elle échange le chlorure extracellulaire contre l'iodure, le formate ou le bicarbonate intracellulaires [3][4][5]. Les fonctions d'échan-geur Cl -/I -et Cl -/HCO 3 -rendent compte des rôles de la pendrine respectivement dans la thyroïde et dans l'oreille interne [6,7].…”

Section: Rôle Dans La Physiologie Rénale Et L'hypertension Artérielleunclassified

“…Cette réabsorption électrogénique de sodium génère un voltage transépithélial (négatif dans la lumière tubulaire par rapport à l'interstitium) qui permet la sécrétion de potassium par couplage de la [15]. Il existe aussi des cellules intercalaires non-A non-B qui expriment à la fois la pompe à proton et l'échangeur Cl -/HCO 3 -à la membrane apicale [14], et dont la fonction reste inconnue à ce jour.…”

Section: Les Multiples Fonctions Du Canal Collecteurunclassified

“…Ces auteurs ont aussi montré que la sécrétion de bicarbonate, mesurée par micro perfusion in vitro, est abolie dans les canaux collecteurs des souris invalidées pour la pendrine, ce qui prouve que la pendrine est l'échangeur Cl -/HCO 3 -apical des cellules intercalaires B [10]. À la suite de cette observation, plusieurs groupes ont étudié la régulation de la pendrine lors de traitements perturbant l'état acide-base.…”

Section: Les Multiples Fonctions Du Canal Collecteurunclassified

See 1 more Smart Citation