The iodide channel of the thyroid: a plasma membrane vesicle study

Golstein, Philippe; Abramow, Maurice; Dumont, Jacques Emile; Beauwens, Robert

doi:10.1152/ajpcell.1992.263.3.c590

Cited by 69 publications

(38 citation statements)

References 22 publications

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“…It is worth noting that this property is one of the major characteristics of dog thyroid cells in primary culture (28). The increased release of 99m TcO 4 Ϫ from the Ca 2ϩ ionophore-stimulated ANO1-expressing HEK 293T and PCCl3 cells is consistent with the very low affinity but sizeable effect of ClO 4 Ϫ , the chemical analog of TcO 4 Ϫ , on the high affinity iodide channel from bovine thyroid membrane vesicles (13,14). A stimulatory effect of Ca 2ϩ ionophore on iodide efflux had already been observed in the FRTL-5 rat thyroid cell line (43).…”

Section: Discussionsupporting

confidence: 54%

Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte

Twyffels

Strickaert

Virreira

et al. 2014

American Journal of Physiology-Cell Physiology

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Iodide is captured by thyrocytes through the Na ϩ /I Ϫ symporter (NIS) before being released into the follicular lumen, where it is oxidized and incorporated into thyroglobulin for the production of thyroid hormones. Several reports point to pendrin as a candidate protein for iodide export from thyroid cells into the follicular lumen. Here, we show that a recently discovered Ca 2ϩ -activated anion channel, TMEM16A or anoctamin-1 (ANO1), also exports iodide from rat thyroid cell lines and from HEK 293T cells expressing human NIS and ANO1. The Ano1 mRNA is expressed in PCCl3 and FRTL-5 rat thyroid cell lines, and this expression is stimulated by thyrotropin (TSH) in rat in vivo, leading to the accumulation of the ANO1 protein at the apical membrane of thyroid follicles. Moreover, ANO1 properties, i.e., activation by intracellular calcium (i.e., by ionomycin or by ATP), low but positive affinity for pertechnetate, and nonrequirement for chloride, better fit with the iodide release characteristics of PCCl3 and FRTL-5 rat thyroid cell lines than the dissimilar properties of pendrin. Most importantly, iodide release by PCCl3 and FRTL-5 cells is efficiently blocked by T16A inh-A01, an ANO1-specific inhibitor, and upon ANO1 knockdown by RNA interference. Finally, we show that the T16A inh-A01 inhibitor efficiently blocks ATP-induced iodide efflux from in vitro-cultured human thyrocytes. In conclusion, our data strongly suggest that ANO1 is responsible for most of the iodide efflux across the apical membrane of thyroid cells.anoctamin-1; iodide release; pendrin; thyrocyte; TMEM16A

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Section: Discussionsupporting

confidence: 54%

Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte

Twyffels

Strickaert

Virreira

et al. 2014

American Journal of Physiology-Cell Physiology

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“…chloride channels, or a second iodide channel. It is noteworthy that studies performed with plasma membrane vesicles suggested the existence of two apical iodide channels (41). One of these channels appears to display a high permeability and specificity for iodide (K m ϳ70 M), whereas the second anion channel has a lower affinity for iodide (K m ϳ33 mM) (41).…”

Section: ) Similar Results Were Observed In Tsa-293 Cells (Results mentioning

confidence: 99%

“…It is noteworthy that studies performed with plasma membrane vesicles suggested the existence of two apical iodide channels (41). One of these channels appears to display a high permeability and specificity for iodide (K m ϳ70 M), whereas the second anion channel has a lower affinity for iodide (K m ϳ33 mM) (41). The pendrin-mediated apical iodide transport shown here, together with the loss of function of pendrin mutations, strongly suggest that pendrin corresponds to one of these channels.…”

Section: ) Similar Results Were Observed In Tsa-293 Cells (Results mentioning

confidence: 99%

Functional Characterization of Pendrin in a Polarized Cell System

Gillam

Sidhaye

Lee

et al. 2004

Journal of Biological Chemistry

142

110

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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.

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“…It was demonstrated to function as an iodide transporter (Taylor et al, 2002;Yoshida et al, 2002). Electrophysiological studies suggest the existence of two apical iodide channels (Golstein et al, 1992), and as recently shown, pendrin mediating vectorial iodide transport corresponds to one of these channels (Gillam et al, 2004). The pendrin gene is not under the control of TSH but it is upregulated by thyroglobulin (Royaux et al, 2000).…”

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confidence: 96%

Expression of pendrin in benign and malignant human thyroid tissues

et al. 2005

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The Pendred syndrome gene (PDS) encodes a transmembrane protein, pendrin, which is expressed in follicular thyroid cells and participates in the apical iodide transport. Pendrin expression has been studied in various thyroid neoplasms by means of immunohistochemistry (IHC), Western blot and RT -quantitative real-time PCR. The expression was related to the functional activity of the thyroid tissue. Follicular cells of normal, nodular goitre and Graves' disease tissues express pendrin at the apical pole of the thyrocytes. In follicular adenomas, pendrin was detected in cell membranes and cytoplasm simultaneously in 10 out of 15 cases. Pendrin protein was detected in 73.3 and 76.7% of the follicular (FTC) and papillary (PTC) thyroid carcinomas, respectively, where pendrin was solely localised inside the cytoplasm. An extensive intracellular immunostaining of pendrin was observed in six out of 11 (54.5%) of positive FTCs and 19 out of 23 (82%) of PTCs. Focal reactivity was detected in one follicular-and three papillary carcinomas, whereas pendrin protein was absent in three of 15 FTC and four of 30 PTC; mRNA of pendrin was detected in 92.4% of thyroid tumours. The relative mRNA expression of pendrin was lower in cancers than in normal thyroid tissues (Po0.001). The pendrin protein level was found to parallel its mRNA expression, which was not, however, related to the tumour size and tumour stage. In conclusion, pendrin is expressed in the majority of differentiated thyroid tumours with high individual variability but its targeting to the apical cell membrane is affected.

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The iodide channel of the thyroid: a plasma membrane vesicle study

Cited by 69 publications

References 22 publications

Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte

Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte

Functional Characterization of Pendrin in a Polarized Cell System

Expression of pendrin in benign and malignant human thyroid tissues

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