TSH regulates pendrin membrane abundance and enhances iodide efflux in thyroid cells.

Details

Serval ID
serval:BIB_6CF855659755
Type
Article: article from journal or magazin.
Collection
Publications
Title
TSH regulates pendrin membrane abundance and enhances iodide efflux in thyroid cells.
Journal
Endocrinology
Author(s)
Pesce L., Bizhanova A., Caraballo J.C., Westphal W., Butti M.L., Comellas A., Kopp P.
ISSN
1945-7170 (Electronic)
ISSN-L
0013-7227
Publication state
Published
Issued date
01/2012
Peer-reviewed
Oui
Volume
153
Number
1
Pages
512-521
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Thyroid hormones are essential for normal development and metabolism. Their synthesis requires transport of iodide into thyroid follicles. The mechanisms involving the apical efflux of iodide into the follicular lumen are poorly elucidated. The discovery of mutations in the SLC26A4 gene in patients with Pendred syndrome (congenital deafness, goiter, and defective iodide organification) suggested a possible role for the encoded protein, pendrin, as an apical iodide transporter. We determined whether TSH regulates pendrin abundance at the plasma membrane and whether this influences iodide efflux. Results of immunoblot and immunofluorescence experiments reveal that TSH and forskolin rapidly increase pendrin abundance at the plasma membrane through the protein kinase A pathway in PCCL-3 rat thyroid cells. The increase in pendrin membrane abundance correlates with a decrease in intracellular iodide as determined by measuring intracellular (125)iodide and can be inhibited by specific blocking of pendrin. Elimination of the putative protein kinase A phosphorylation site T717A results in a diminished translocation to the membrane in response to forskolin. These results demonstrate that pendrin translocates to the membrane in response to TSH and suggest that it may have a physiological role in apical iodide transport and thyroid hormone synthesis.
Keywords
Animals, Cell Line, Cell Membrane/metabolism, Chloride-Bicarbonate Antiporters/genetics, Chloride-Bicarbonate Antiporters/metabolism, Colforsin/pharmacology, Cyclic AMP-Dependent Protein Kinases/genetics, Cyclic AMP-Dependent Protein Kinases/metabolism, Goiter, Nodular/genetics, Goiter, Nodular/metabolism, Hearing Loss, Sensorineural/genetics, Hearing Loss, Sensorineural/metabolism, Humans, Iodides/metabolism, Ion Transport/drug effects, Membrane Transport Proteins/genetics, Membrane Transport Proteins/metabolism, Mutagenesis, Site-Directed, Phosphorylation, Rats, Recombinant Proteins/genetics, Recombinant Proteins/metabolism, Signal Transduction, Sulfate Transporters, Thyroid Gland/drug effects, Thyroid Gland/metabolism, Thyrotropin/metabolism, Thyrotropin/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
27/12/2020 23:26
Last modification date
28/12/2020 6:26
Usage data