BACKGROUND/AIMS: Iodide efflux from thyroid cells into the follicular lumen is essential for the synthesis of thyroid hormones, however, the pathways mediating this transport have only been partially identified. A calcium-activated pathway of iodide efflux has long been recognized, but its molecular identity unknown. Anoctamin 1 (ANO1) is a calcium-activated chloride channel (CaCC), and this study aims to investigate its contribution to iodide fluxes in thyroid cells. METHODS: RT-PCR, immunohistochemistry, and live cell imaging with the fluorescent halide biosensor YFP-H148Q/I152L were used to study the expression, localization and function of ANO1 in thyroid cells. RESULTS: ANO1 mRNA was detected in human thyroid tissue and FRTL-5 thyrocytes, and ANO1 protein was localized to the apical membrane of follicular cells. ATP induced a transient loss of iodide from FRTL-5 cells that was dependent on the mobilization of intracellular calcium, and was inhibited by CaCC/ANO1 inhibitors and siRNA against ANO1. Calcium-activated iodide efflux was also observed in CHO cells over-expressing the Sodium Iodide Symporter (NIS) and ANO1. CONCLUSION: ANO1 in thyrocytes functions as a calcium-activated channel mediating iodide efflux, and may contribute to the rapid delivery of iodide into the follicular lumen for the synthesis of thyroid hormones following activation by calcium-mobilizing stimuli.
Titolo: | Anoctamin 1 is apically expressed on thyroid follicular cells and contributes to ATP- and calcium-activated iodide efflux. |
Autore/i: | Iosco C; Cosentino C; Sirna L; Romano R; Cursano S; Mongia A; Pompeo G; di Bernardo J; CECCARELLI, CLAUDIO; TALLINI, GIOVANNI; RHODEN, KERRY JANE |
Autore/i Unibo: | |
Anno: | 2014 |
Rivista: | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1159/000366313 |
Abstract: | BACKGROUND/AIMS: Iodide efflux from thyroid cells into the follicular lumen is essential for the synthesis of thyroid hormones, however, the pathways mediating this transport have only been partially identified. A calcium-activated pathway of iodide efflux has long been recognized, but its molecular identity unknown. Anoctamin 1 (ANO1) is a calcium-activated chloride channel (CaCC), and this study aims to investigate its contribution to iodide fluxes in thyroid cells. METHODS: RT-PCR, immunohistochemistry, and live cell imaging with the fluorescent halide biosensor YFP-H148Q/I152L were used to study the expression, localization and function of ANO1 in thyroid cells. RESULTS: ANO1 mRNA was detected in human thyroid tissue and FRTL-5 thyrocytes, and ANO1 protein was localized to the apical membrane of follicular cells. ATP induced a transient loss of iodide from FRTL-5 cells that was dependent on the mobilization of intracellular calcium, and was inhibited by CaCC/ANO1 inhibitors and siRNA against ANO1. Calcium-activated iodide efflux was also observed in CHO cells over-expressing the Sodium Iodide Symporter (NIS) and ANO1. CONCLUSION: ANO1 in thyrocytes functions as a calcium-activated channel mediating iodide efflux, and may contribute to the rapid delivery of iodide into the follicular lumen for the synthesis of thyroid hormones following activation by calcium-mobilizing stimuli. |
Data prodotto definitivo in UGOV: | 2014-11-04 16:02:34 |
Data stato definitivo: | 2016-01-17T12:52:18Z |
Appare nelle tipologie: | 1.01 Articolo in rivista |