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This Article Full Text Full Text (PDF) Supplementary figures All Versions of this Article: JOE-08-0249v1 199/2/213    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wu, S.-L. Articles by Hsiang, C.-Y. PubMed PubMed Citation Articles by Wu, S.-L. Articles by Hsiang, C.-Y.

Department of Biochemistry, China Medical University, 91 Hsueh-Shih Road, Taichung 40402, Taiwan, ROC¹ Graduate Institute of Chinese Medical Science, China Medical University, Taichung 40402, Taiwan, ROC² Nuclear Medicine and PET Center³ Department of Radiation Therapy and Oncology, China Medical University Hospital, Taichung 40447, Taiwan, ROC⁴ Department of Microbiology, China Medical University, 91 Hsueh-Shih Road, Taichung 40402, Taiwan, ROC

(Correspondence should be addressed to C-Y Hsiang; Email: cyhsiang{at}mail.cmu.edu.tw)

The sodium/iodide symporter (SLC5A5; also known as NIS), a transmembrane glycoprotein principally in the thyroid gland, is responsible for the accumulation of iodide necessary for thyroid hormones. Our previous study indicated that a novel exon 6 deletion (residues 233–280) in SLC5A5 loses the iodide uptake activity. Herein we characterized the role of His-226 in iodide transport of SLC5A5. His-226, a highly conserved extracellular residue among SLC5A5 homologs, was replaced with alanine, aspartic acid, glutamic acid, or lysine. All the SLC5A5 mutants were expressed normally in the cells and targeted correctly to the plasma membrane. However, all of the mutants displayed severe defects in iodide uptake, suggesting that His-226 was critical for iodide uptake. Kinetic analysis further showed that mutation at His-226 led to a dramatic decrease in V_max. These findings suggested that the decreased levels of iodide uptake activity of SLC5A5 mutants resulted from lower catalytic rates. In conclusion, our data first identified the involvement of extracellular charged amino acid residue in the iodide uptake ability of SLC5A5.