This Article Full Text Full Text (PDF) All Versions of this Article: 19/11/2847    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De la Vieja, A. Articles by Carrasco, N. Search for Related Content PubMed PubMed Citation Articles by De la Vieja, A. Articles by Carrasco, N.

Molecular Analysis of a Congenital Iodide Transport Defect: G543E Impairs Maturation and Trafficking of the Na⁺/I^– Symporter

Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461

Address all correspondence and requests for reprints to: Nancy Carrasco, Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461. E-mail: carrasco{at}aecom.yu.edu.

The Na⁺/I^– symporter (NIS) is a key membrane glycoprotein that mediates active I^– transport in the thyroid and other tissues. Upon isolation of the cDNA encoding NIS, 10 NIS mutations that cause congenital iodide transport defect have been identified. Three of these mutations (T354P, G395R, and Q267E) have been thoroughly characterized at the molecular level. All three NIS mutant proteins are correctly targeted to the plasma membrane; however, whereas Q267E displays minimal activity, T354P and G395R are inactive. Here, we show that in contrast to these mutants, G543E NIS matures only partially and is retained intracellularly; thus, it is not targeted properly to the cell surface, apparently because of faulty folding. These findings indicate that the G543 residue plays significant roles in NIS maturation and trafficking. Remarkably, NIS activity was rescued by small neutral amino acid substitutions (volume < 129 ų) at this position, suggesting that G543 is in a tightly packed region of NIS.

This article has been cited by other articles:

				S.-L. Wu, T.-Y. Ho, J.-A. Liang, and C.-Y. Hsiang Histidine residue at position 226 is critical for iodide uptake activity of human sodium/iodide symporter J. Endocrinol., November 1, 2008; 199(2): 213 - 219. [Abstract] [Full Text] [PDF]

				M. D. Reed-Tsur, A. De la Vieja, C. S. Ginter, and N. Carrasco Molecular Characterization of V59E NIS, a Na+/I- Symporter Mutant that Causes Congenital I- Transport Defect Endocrinology, June 1, 2008; 149(6): 3077 - 3084. [Abstract] [Full Text] [PDF]

				M. Dayem, C. Basquin, V. Navarro, P. Carrier, R. Marsault, P. Chang, S. Huc, E. Darrouzet, S. Lindenthal, and T. Pourcher Comparison of expressed human and mouse sodium/iodide symporters reveals differences in transport properties and subcellular localization J. Endocrinol., April 1, 2008; 197(1): 95 - 109. [Abstract] [Full Text] [PDF]

				A. De la Vieja, M. D. Reed, C. S. Ginter, and N. Carrasco Amino Acid Residues in Transmembrane Segment IX of the Na+/I Symporter Play a Role in Its Na+ Dependence and Are Critical for Transport Activity J. Biol. Chem., August 31, 2007; 282(35): 25290 - 25298. [Abstract] [Full Text] [PDF]

				G. Riesco-Eizaguirre and P. Santisteban A perspective view of sodium iodide symporter research and its clinical implications. Eur. J. Endocrinol., October 1, 2006; 155(4): 495 - 512. [Abstract] [Full Text] [PDF]

				G. Szinnai, S. Kosugi, C. Derrien, N. Lucidarme, V. David, P. Czernichow, and M. Polak Extending the Clinical Heterogeneity of Iodide Transport Defect (ITD): A Novel Mutation R124H of the Sodium/Iodide Symporter Gene and Review of Genotype-Phenotype Correlations in ITD J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1199 - 1204. [Abstract] [Full Text] [PDF]