title: Anoctamin 1 is apically expressed on thyroid follicular cells and contributes to ATP- and calcium-activated iodide efflux.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical Genetics Unit, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Iosco
authors.forename: Cristina
authors.initials: C
authors.lastname: Cosentino
authors.forename: Laura
authors.initials: L
authors.lastname: Sirna
authors.forename: Roberta
authors.initials: R
authors.lastname: Romano
authors.forename: Silvia
authors.initials: S
authors.lastname: Cursano
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mongia
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Pompeo
authors.forename: Julie
authors.initials: J
authors.lastname: di Bernardo
authors.forename: Claudio
authors.initials: C
authors.lastname: Ceccarelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tallini
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Rhoden
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000075369:Anoctamin-1; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D007454:Iodides / Q000378:metabolism*; D017136:Ion Transport; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*
chemical_list: C552942:ANO1 protein, rat; D000075369:Anoctamin-1; D018118:Chloride Channels; D007454:Iodides; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D002118:Calcium