ArticleJournal of cell science2013
The iodide-transport-defect-causing mutation R124H: a δ-amino group at position 124 is critical for maturation and trafficking of the Na+/I- symporter.
Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- New Insights into Iodide Transport Defects (ITDs) from the Characterization of a Heterozygous NIS Missense Variant (p.G288S) Identified in a Family with Thyroid Dysfunction During Pregnancy.International journal of molecular sciences · 2026Article
- Molecular Mechanisms of Radioiodine Refractoriness in Differentiated Thyroid Cancer: Focus on Sodium/Iodide Symporter Dysregulation.Current issues in molecular biology · 2026Review
- Basolateral Sorting of the Sodium/Iodide Symporter Is Mediated by Adaptor Protein 1 Clathrin Adaptor Complexes.Thyroid : official journal of the American Thyroid Association · 2022Article
- The Iodide Transport Defect-Causing Y348D Mutation in the NaThyroid : official journal of the American Thyroid Association · 2021Article
- A Novel SLC5A5 Variant Reveals the Crucial Role of Kinesin Light Chain 2 in Thyroid Hormonogenesis.The Journal of clinical endocrinology and metabolism · 2021Article
- Novel Compound Heterozygous Pathogenic Mutations ofFrontiers in endocrinology · 2021Article
- Review
- Mapping of Ion and Substrate Binding Sites in Human Sodium Iodide Symporter (hNIS).Journal of chemical information and modeling · 2020Article
- Implications of NaJournal of the Endocrine Society · 2019Review
- A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I- Symporter.Endocrinology · 2019Article
- Defects of Thyroid Hormone Synthesis and Action.Endocrinology and metabolism clinics of North America · 2017Review
- The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications.Annual review of physiology · 2017Review
- Na+ coordination at the Na2 site of the Na+/I- symporter.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Sodium/Iodide Symporter Mutant V270E Causes Stunted Growth but No Cognitive Deficiency.The Journal of clinical endocrinology and metabolism · 2015Article
- Beyond non-integer Hill coefficients: A novel approach to analyzing binding data, applied to Na+-driven transporters.The Journal of general physiology · 2015Article
- Physiological sodium concentrations enhance the iodide affinity of the Na+/I- symporter.Nature communications · 2014Article
- The Na+/I- symporter (NIS): mechanism and medical impact.Endocrine reviews · 2014Review
- Asn441 plays a key role in folding and function of the Na+/I- symporter (NIS).FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Na(+)/I(-) symporter (NIS)-mediated active accumulation of I(-) in thyrocytes is a key step in the biosynthesis of the iodine-containing thyroid hormones T3 and T4. Several NIS mutants have been identified as a cause of congenital I(-) transport defect (ITD), and their investigation has yielded valuable mechanistic information on NIS. Here we report novel findings derived from the thorough characterization of the ITD-causing mutation R124H, located in the second intracellular loop (IL-2). R124H NIS is incompletely glycosylated and colocalizes with endoplasmic reticulum (ER)-resident protein markers. As a result, R124H NIS is not targeted to the plasma membrane and therefore does not mediate any I(-) transport in transfected COS-7 cells. Strikingly, however, the mutant is intrinsically active, as revealed by its ability to mediate I(-) transport in membrane vesicles. Of all the amino acid substitutions we carried out at position 124 (K, D, E, A, W, N and Q), only Gln restored targeting of NIS to the plasma membrane and NIS activity, suggesting a key structural role for the δ-amino group of R124 in the transporter's maturation and cell surface targeting. Using our NIS homology model based on the structure of the Vibrio parahaemolyticus Na(+)/galactose symporter, we propose an interaction between the δ-amino group of either R or Q124 and the thiol group of C440, located in IL-6. We conclude that the interaction between IL-2 and IL-6 is critical for the local folding required for NIS maturation and plasma membrane trafficking.
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