The sodium–iodide symporter (NIS) is an integral membrane protein that plays a crucial role in iodide accumulation, especially in the thyroid. As for many other membrane proteins, its intracellular sorting and distribution have a tremendous effect on its function, and constitute an important aspect of its regulation. Many short sequences have been shown to contribute to protein trafficking along the sorting or endocytic pathways. Using bioinformatics tools, we identified such potential sites on human NIS [tyrosine-based motifs, SH2-(Src homology 2), SH3- and PDZ (post-synaptic density-95/discs large tumour suppressor/zonula occludens-1)-binding motifs, and diacidic, dibasic and dileucine motifs] and analysed their roles using mutagenesis. We found that several of these sites play a role in protein stability and/or targeting to the membrane. Aside from the mutation at position 178 (SH2 plus tyrosine-based motif) that affects iodide uptake, the most drastic effect is associated with the mutation of an internal PDZ-binding motif at position 121 that completely abolishes NIS expression at the plasma membrane. Mutating the sites located on the C-terminal domain of the protein has no effect except for the creation of a diacidic motif that decreases the total NIS protein level without affecting its expression at the plasma membrane.
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Research Article|
March 29 2016
A systematic evaluation of sorting motifs in the sodium–iodide symporter (NIS)
Elisabeth Darrouzet;
Elisabeth Darrouzet
1
*Laboratoire TIRO, CEA, iBEB, SBTN, centre de Marcoule, 30207 Bagnols sur Cèze, France
1To whom correspondence should be addressed (email elisabeth.darrouzet@cea.fr).
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Fanny Graslin;
Fanny Graslin
†Laboratoire TIRO, CEA, Faculté de médecine, 28 Avenue de Valombrose, 06107 Nice, France
‡Laboratoire TIRO, Université de Nice Sophia Antipolis, Faculté de médecine, 28 Avenue de Valombrose, 06107 Nice, France
§Centre Antoine Lacassagne, 33 Avenue de Valombrose, 06100 Nice, France
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Didier Marcellin;
Didier Marcellin
*Laboratoire TIRO, CEA, iBEB, SBTN, centre de Marcoule, 30207 Bagnols sur Cèze, France
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Iulia Tcheremisinova;
Iulia Tcheremisinova
†Laboratoire TIRO, CEA, Faculté de médecine, 28 Avenue de Valombrose, 06107 Nice, France
‡Laboratoire TIRO, Université de Nice Sophia Antipolis, Faculté de médecine, 28 Avenue de Valombrose, 06107 Nice, France
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Charles Marchetti;
Charles Marchetti
║Laboratoire LI2D, CEA, iBiTECS, SPI, centre de Marcoule, 30207 Bagnols sur Cèze, France
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Lisa Salleron;
Lisa Salleron
†Laboratoire TIRO, CEA, Faculté de médecine, 28 Avenue de Valombrose, 06107 Nice, France
‡Laboratoire TIRO, Université de Nice Sophia Antipolis, Faculté de médecine, 28 Avenue de Valombrose, 06107 Nice, France
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Philippe Pognonec;
Philippe Pognonec
†Laboratoire TIRO, CEA, Faculté de médecine, 28 Avenue de Valombrose, 06107 Nice, France
‡Laboratoire TIRO, Université de Nice Sophia Antipolis, Faculté de médecine, 28 Avenue de Valombrose, 06107 Nice, France
¶CNRS, Délégation Côte d'Azur, 250 rue Albert Einstein, 06905 Sophia Antipolis, France
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Thierry Pourcher
Thierry Pourcher
†Laboratoire TIRO, CEA, Faculté de médecine, 28 Avenue de Valombrose, 06107 Nice, France
‡Laboratoire TIRO, Université de Nice Sophia Antipolis, Faculté de médecine, 28 Avenue de Valombrose, 06107 Nice, France
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Publisher: Portland Press Ltd
Received:
October 16 2015
Revision Received:
January 19 2016
Accepted:
February 01 2016
Accepted Manuscript online:
February 01 2016
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 Authors; published by Portland Press Limited
2016
Biochem J (2016) 473 (7): 919–928.
Article history
Received:
October 16 2015
Revision Received:
January 19 2016
Accepted:
February 01 2016
Accepted Manuscript online:
February 01 2016
Citation
Elisabeth Darrouzet, Fanny Graslin, Didier Marcellin, Iulia Tcheremisinova, Charles Marchetti, Lisa Salleron, Philippe Pognonec, Thierry Pourcher; A systematic evaluation of sorting motifs in the sodium–iodide symporter (NIS). Biochem J 1 April 2016; 473 (7): 919–928. doi: https://doi.org/10.1042/BJ20151086
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