ArticleEndocrinology2019
A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I- Symporter.
Article in Endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 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
- Combined Vorinostat and Chloroquine Inhibit Sodium-Iodide Symporter Endocytosis and Enhance Radionuclide Uptake In Vivo.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Functional characterization of novel compound heterozygous missenseFrontiers in endocrinology · 2024Article
- Sequence and structural insights of monoleucine-based sorting motifs contained within the cytoplasmic domains of basolateral proteins.Frontiers in cell and developmental biology · 2024Review
- Advances in the molecular mechanism and targeted therapy of radioactive-iodine refractory differentiated thyroid cancer.Medical oncology (Northwood, London, England) · 2023Review
- The master role of polarized NIS expression in regulating iodine metabolism in the human body.Archives of endocrinology and metabolism · 2023Article
- 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
- Targeted Next-Generation Sequencing of Congenital Hypothyroidism-Causative Genes Reveals Unexpected Thyroglobulin Gene Variants in Patients with Iodide Transport Defect.International journal of molecular sciences · 2022Article
- Article
- XB130 Plays an Essential Role in Folliculogenesis Through Mediating Interactions Between Microfilament and Microtubule Systems in Thyrocytes.Thyroid : official journal of the American Thyroid Association · 2022Article
- Capsaicin restores sodium iodine symporter-mediated radioiodine uptake through bypassing canonical TSH‒TSHR pathway in anaplastic thyroid carcinoma cells.Journal of molecular cell biology · 2022Article
- Silent but Not Harmless: A SynonymousFrontiers in endocrinology · 2022Article
- PolarProtPred: predicting apical and basolateral localization of transmembrane proteins using putative short linear motifs and deep learning.Bioinformatics (Oxford, England) · 2021Article
- XB130 Deficiency Causes Congenital Hypothyroidism in Mice due to Disorganized Apical Membrane Structure and Function of Thyrocytes.Thyroid : 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
- Tumor microenvironment affects exogenous sodium/iodide symporter expression.Translational oncology · 2021Article
- Implications of NaJournal of the Endocrine Society · 2019Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
The Na+/iodide (I-) symporter (NIS), a glycoprotein expressed at the basolateral plasma membrane of thyroid follicular cells, mediates I- accumulation for thyroid hormonogenesis and radioiodide therapy for differentiated thyroid carcinoma. However, differentiated thyroid tumors often exhibit lower I- transport than normal thyroid tissue (or even undetectable I- transport). Paradoxically, the majority of differentiated thyroid cancers show intracellular NIS expression, suggesting abnormal targeting to the plasma membrane. Therefore, a thorough understanding of the mechanisms that regulate NIS plasma membrane transport would have multiple implications for radioiodide therapy. In this study, we show that the intracellularly facing carboxy-terminus of NIS is required for the transport of the protein to the plasma membrane. Moreover, the carboxy-terminus contains dominant basolateral information. Using internal deletions and site-directed mutagenesis at the carboxy-terminus, we identified a highly conserved monoleucine-based sorting motif that determines NIS basolateral expression. Furthermore, in clathrin adaptor protein (AP)-1B-deficient cells, NIS sorting to the basolateral plasma membrane is compromised, causing the protein to also be expressed at the apical plasma membrane. Computer simulations suggest that the AP-1B subunit σ1 recognizes the monoleucine-based sorting motif in NIS carboxy-terminus. Although the mechanisms by which NIS is intracellularly retained in thyroid cancer remain elusive, our findings may open up avenues for identifying molecular targets that can be used to treat radioiodide-refractory thyroid tumors that express NIS intracellularly.
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