ArticleProceedings of the National Academy of Sciences of the United States of America2011
Mechanism of anion selectivity and stoichiometry of the Na+/I- symporter (NIS).
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 61 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
- Functional characterization of novel compound heterozygous missenseFrontiers in endocrinology · 2024Article
- The master role of polarized NIS expression in regulating iodine metabolism in the human body.Archives of endocrinology and metabolism · 2023Article
- Sodium/Iodide Symporter Metastable Intermediates Provide Insights into Conformational Transition between Principal Thermodynamic States.The journal of physical chemistry. B · 2023Article
- 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
- Review
- Novel Compound Heterozygous Pathogenic Mutations ofFrontiers in endocrinology · 2021Article
- Sodium-coupled glucose transport, the SLC5 family, and therapeutically relevant inhibitors: from molecular discovery to clinical application.Pflugers Archiv : European journal of physiology · 2020Review
- Allosteric regulation of mammalian NaNature structural & molecular biology · 2020Article
- Mapping of Ion and Substrate Binding Sites in Human Sodium Iodide Symporter (hNIS).Journal of chemical information and modeling · 2020Article
- Inter-species variation in monovalent anion substrate selectivity and inhibitor sensitivity in the sodium iodide symporter (NIS).PloS one · 2020Article
- How Non-invasiveFrontiers in physiology · 2020Review
- Insights into major facilitator superfamily domain-containing protein-2a (Mfsd2a) in physiology and pathophysiology. What do we know so far?Journal of neuroscience research · 2020Review
- A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I- Symporter.Endocrinology · 2019Article
- Implications of NaJournal of the Endocrine Society · 2019Review
- Iodide Binding in Sodium-Coupled Cotransporters.Journal of chemical information and modeling · 2017Article
- An extremely high dietary iodide supply forestalls severe hypothyroidism in NaScientific reports · 2017Article
- 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
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
I(-) uptake in the thyroid, the first step in thyroid hormone biosynthesis, is mediated by the Na(+)/I(-) symporter (NIS) with an electrogenic 2Na(+):1I(-) stoichiometry. We have obtained mechanistic information on NIS by characterizing the congenital I(-) transport defect-causing NIS mutant G93R. This mutant is targeted to the plasma membrane but is inactive. Substitutions at position 93 show that the longer the side chain of the neutral residue at this position, the higher the K(m) for the anion substrates. Unlike WT NIS, which mediates symport of Na(+) and the environmental pollutant perchlorate electroneutrally, G93T/N/Q/E/D NIS, strikingly, do it electrogenically with a 21 stoichiometry. Furthermore, G93E/Q NIS discriminate between anion substrates, a discovery with potential clinical relevance. A 3D homology model of NIS based on the structure of the bacterial Na(+)/galactose transporter identifies G93 as a critical player in the mechanism of the transporter: the changes from an outwardly to an inwardly open conformation during the transport cycle use G93 as a pivot.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.