The sodium/iodide symporter (NIS or SLC5A5) is an intrinsic membrane protein implicated in iodide uptake into thyroid follicular cells. It plays a crucial role in iodine metabolism and thyroid regulation and its function is widely exploited in the diagnosis and treatment of benign and malignant thyroid diseases. A great effort is currently being made to develop a NIS-based gene therapy also allowing the radiotreatment of nonthyroidal tumors. NIS is also expressed in other tissues, such as salivary gland, stomach and mammary gland during lactation, where its physiological role remains unclear. The molecular identity of the thyroid iodide transporter was elucidated approximately fifteen years ago. It belongs to the superfamily of sodium/solute symporters, SSS (and to the human transporter family, SLC5), and is composed of 13 transmembrane helices and 643 amino acid residues in humans. Knowledge concerning NIS structure/function relationship has been obtained by taking advantage of the high resolution structure of one member of the SSS family, the Vibrio parahaemolyticus sodium/galactose symporter (vSGLT), and from studies of gene mutations leading to congenital iodine transport defects (ITD). This review will summarize current knowledge regarding the molecular characterization of NIS.
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http://dx.doi.org/10.1016/j.bbamem.2013.08.013 | DOI Listing |
Chemosphere
January 2025
Department of Environmental Science, Baylor University, Waco, TX, USA. Electronic address:
Background: Perchlorate, nitrate, and thiocyanate are well-known sodium/iodide symporter (NIS) inhibitors that disturb iodide uptake at the thyroid, affecting thyroid function. However, the associations between NIS inhibitor exposure and thyroid function are not well summarized in humans.
Objective: We aimed to summarize associations between NIS inhibitor exposure and thyroid function markers and to identify key information gaps for future studies.
Environ Pollut
January 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China; Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address:
Differentiated thyroid cancer (DTC) generally has a favorable prognosis, and radioactive iodine (RAI) therapy is typically used for metastatic DTC that continues to progress and poses life-threatening risks. However, resistance to RAI in metastatic DTC significantly impairs treatment effectiveness. This study aims to identify potential compounds that may influence RAI efficacy.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
January 2025
Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Introduction: The sodium/iodide symporter (NIS) mediates active iodide accumulation in the thyroid follicular cell. Biallelic loss-of-function variants in the NIS-coding gene cause congenital dyshormonogenic hypothyroidism due to a defect in the accumulation of iodide, which is required for thyroid hormonogenesis.
Objective: We aimed to identify, and if so to functionally characterize, novel pathogenic gene variants in a patient diagnosed with severe congenital dyshormonogenic hypothyroidism characterized by undetectable radioiodide accumulation in a eutopic thyroid gland, as well as in the salivary glands.
Unlabelled: We report here transport of the Epidermal Growth Factor Receptor (EGFR), Insulin Receptor, 7-pass transmembrane receptor Smoothened, and 13-pass Sodium-iodide symporter to extracellular vesicles (EVs) for structural and functional studies. Mass spectrometry confirmed the transported proteins as the most abundant in EV membranes, and the presence of many receptor-interacting proteins demonstrates the utility of EVs for characterizing membrane protein interactomes. Cryo-electron tomography of EGFR-containing EVs reveals that EGFR forms clusters in the presence of EGF with a ∼3 nm gap between the inner membrane and cytoplasmic density.
View Article and Find Full Text PDFALTEX
December 2024
KaLy-Cell SAS, Plobsheim, France.
The effects of ten test chemicals towards thyroid sodium-iodide symporter (NIS), thyroid peroxidase (TPO), and deiodinases (DIOs) type I, II, and III were evaluated in in vitro rat and human systems and compared. Test chemicals known to directly affect TH levels in vivo were confirmed to effectively inhibit at least one of the tested in vitro endpoints, without significant disparities between species, and the tested compounds known to not affect thyroid function, were found ineffective. Interestingly, Iodide Transport Blocker 5, a potent non-competitive iodine uptake inhibitor, exhibited effects beyond direct NIS inhibition, by impacting NIS function through ATP depletion, and also inhibited TPO and DIO1/2 enzymes, although to a lesser extent.
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