CoChat
Sign Up
Cited by 298Thyroid Disorders and TreatmentsThyroid Cancer Diagnosis and TreatmentChemical Analysis and Environmental Impact

The Sodium/Iodide symporter (NIS): Molecular physiology and preclinical and clinical applications

Open access
Ravera, Silvia, Reyna-Neyra, Andrea, Ferrandino, Giuseppe, Amzel, L. Mario, Carrasco, Nancy·2017·Annual Review of Physiology
DOI 10.1146/annurev-physiol-022516-034125PMC PMC5739519
Open this paper in CoChat — free accountOpen PDF

Abstract

Active iodide (I − ) transport in both the thyroid and some extrathyroidal tissues is mediated by the Na + /I − symporter (NIS). In the thyroid, NIS-mediated I − uptake plays a pivotal role in thyroid hormone (TH) biosynthesis. THs are key during embryonic and postembryonic development and critical for cell metabolism at all stages of life. The molecular characterization of NIS in 1996 and the use of radioactive I − isotopes have led to significant advances in the diagnosis and treatment of thyroid cancer and provide the molecular basis for studies aimed at extending the use of radioiodide treatment in extrathyroidal malignancies. This review focuses on the most recent findings on I − homeostasis and I − transport deficiency-causing NIS mutations, as well as current knowledge of the structure/function properties of NIS and NIS regulatory mechanisms. We also discuss employing NIS as a reporter gene using viral vectors and stem cells in imaging, diagnostic, and therapeutic procedures.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1146/annurev-physiol-022516-034125

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Uptake of circulating I- by thyroid follicles is mediated by the Na+/I- symporter (NIS), a glycoprotein located on the basolateral plasma membrane of thyrocytes and encoded by SLC5A5.

    “Uptake of circulating I- by thyroid follicles is mediated by the Na+/I- symporter (NIS), a glycoprotein located on the basolateral plasma membrane of the thyrocytes and encoded by the solute carrier family 5 member 5 (SLC5A5) gene (51).”

    From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [51]

    The Introduction states that NIS is a plasma-membrane glycoprotein that transports iodide into the thyroid. The Molecular Characterization and Iodide Transport Defect sections identify NIS as SLC5A5 and state that the SLC5A5 gene encodes it. Our copy does not specify that NIS is on the basolateral membrane of thyrocytes; its explicit basolateral examples concern other tissues. Page numbers are unavailable in the indexed copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 161

  1. [4]Seidlin SM Marinelli LD Oshry E 1946 Radioactive iodine therapy: effect on functioning metastases of adenocarcinoma of the thyroid JAMA 132 838 47 20274882
  2. [5]Dai G Levy O Carrasco N 1996 Cloning and characterization of the thyroid iodide transporter Nature 379 458 60 8559252
  3. [6]Eskandari S Loo DD Dai G Levy O Wright EM Carrasco N 1997 Thyroid Na+/I− symporter. Mechanism, stoichiometry, and specificity J Biol Chem 272 27230 38 9341168
  4. [7]Tazebay UH Wapnir IL Levy O Dohán O Zuckier LS 2000 The mammary gland iodide transporter is expressed during lactation and in breast cancer Nat Med 6 871 78 10932223
  5. [8]Wapnir IL van de Rijn M Nowels K Amenta PS Walton K 2003 Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas using high density tissue microarrays and conventional sections J Clin Endocrinol Metab 88 1880 88 12679487
  6. [9]Paroder-Belenitsky M Maestas MJ Dohán O Nicola JP Reyna-Neyra A 2011 Mechanism of anion selectivity and stoichiometry of the Na+/I− symporter (NIS) PNAS 108 17933 38 22011571 PMC3207644
  7. [10]Dohán O Portulano C Basquin C Reyna-Neyra A Amzel LM Carrasco N 2007 The Na+/I− symporter (NIS) mediates electroneutral active transport of the environmental pollutant perchlorate PNAS 104 20250 55 18077370 PMC2154417
  8. [11]Miller A Russell SJ 2016 The use of the NIS reporter gene for optimizing oncolytic virotherapy Expert Opin Biol Ther 16 15 32 26457362 PMC4732458
  9. [12]Penheiter AR Griesmann GE Federspiel MJ Dingli D Russell SJ Carlson SK 2012 Pinhole micro-SPECT/CT for noninvasive monitoring and quantitation of oncolytic virus dispersion and percent infection in solid tumors Gene Ther 19 279 87 21753796 PMC3198860
  10. [14]Portulano C Paroder-Belenitsky M Carrasco N 2014 The Na+/I− symporter (NIS): mechanism and medical impact Endocr Rev 35 106 49 24311738 PMC3895864
  11. [15]Bassett JH Williams GR 2016 Role of thyroid hormones in skeletal development and bone maintenance Endocr Rev 37 135 87 26862888 PMC4823381
  12. [16]Videla LA Fernández V Cornejo P Vargas R Castillo I 2015 Thyroid hormone in the frontier of cell protection, survival and functional recovery Expert Rev Mol Med 17 e10 26004623
  13. [17]Dunn JT Delange F 2001 Damaged reproduction: the most important consequence of iodine deficiency J Clin Endocrinol Metab 86 2360 63 11397823
  14. [18]Morreale de Escobar G Obregón MJ Escobar del Rey F 2000 Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia? J Clin Endocrinol Metab 85 3975 87 11095417
  15. [19]Verheesen RH Schweitzer CM 2008 Iodine deficiency, more than cretinism and goiter Med Hypotheses 71 645 48 18703293
  16. [20]Ivanova L Zandberga E Siliņa K Kalniņa Z Abols A 2015 Prognostic relevance of carbonic anhydrase IX expression is distinct in various subtypes of breast cancer and its silencing suppresses self-renewal capacity of breast cancer cells Cancer Chemother Pharmacol 75 235 46 25422154
  17. [21]World Health Org (WHO) 2014 Guideline: Fortification of Food-Grade Salt with Iodine for the Prevention and Control of Iodine Deficiency Disorders Geneva WHO 25473709
  18. [22]Wolff J 1964 Transport of iodide and other anions in the thyroid gland Physiol Rev 44 45 90 14105583
  19. [23]Smanik PA Liu Q Furminger TL Ryu K Xing S 1996 Cloning of the human sodium iodide symporter Biochem Biophys Res Commun 226 339 45 8806637
  20. [24]Smanik PA Ryu KY Theil KS Mazzaferri EL Jhiang SM 1997 Expression, exon-intron organization, and chromosome mapping of the human sodium iodide symporter Endocrinology 138 3555 58 9231811
  21. [25]Levy O Dai G Riedel C Ginter CS Paul EM 1997 Characterization of the thyroid Na+/I− symporter with an anti-COOH terminus antibody PNAS 94 5568 73 9159113 PMC20819
  22. [26]Levy O De la Vieja A Carrasco N 1998 The Na+/I− symporter (NIS): recent advances J Bioenerg Biomembr 30 195 206 9672241
  23. [27]Faham S Watanabe A Besserer GM Cascio D Specht A 2008 The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+/sugar symport Science 321 810 14 18599740 PMC3654663
  24. [28]Levy O De la Vieja A Ginter CS Riedel C Dai G Carrasco N 1998 N-linked glycosylation of the thyroid Na+/I− symporter (NIS). Implications for its secondary structure model J Biol Chem 273 22657 63 9712895
  25. [29]Li W Nicola JP Amzel LM Carrasco N 2013 Asn441 plays a key role in folding and function of the Na+/I− symporter (NIS) FASEB J 27 3229 38 23650190 PMC3714583
  26. [30]Nicola JP Carrasco N Mario Amzel L 2014 Physiological sodium concentrations enhance the iodide affinity of the Na+/I− symporter Nat Commun 5 3948 24888603 PMC4248369
  27. [31]Kogai T Endo T Saito T Miyazaki A Kawaguchi A Onaya T 1997 Regulation by thyroid-stimulating hormone of sodium/iodide symporter gene expression and protein levels in FRTL-5 cells Endocrinology 138 2227 32 9165005
  28. [32]Marcocci C Cohen JL Grollman EF 1984 Effect of actinomycin D on iodide transport in FRTL-5 thyroid cells Endocrinology 115 2123 32 6499763
  29. [33]Riedel C Levy O Carrasco N 2001 Post-transcriptional regulation of the sodium/iodide symporter by thyrotropin J Biol Chem 276 21458 63 11290744
  30. [34]Saito T Endo T Kawaguchi A Ikeda M Nakazato M 1997 Increased expression of the Na+/I− symporter in cultured human thyroid cells exposed to thyrotropin and in Graves’ thyroid tissue J Clin Endocrinol Metab 82 3331 36 9329364
  31. [35]Weiss SJ Philp NJ Grollman EF 1984 Iodide transport in a continuous line of cultured cells from rat thyroid Endocrinology 114 1090 98 6705729
  32. [36]Carrasco N 2013 Thyroid hormones synthesis: thyroid iodide transport The Thyroide A Fundamental and Clinical Text Braverman LE Cooper DS 32 47 Philadelphia, PA Lippincott Williams & Wilkins
  33. [37]Wolff J Chaikoff IL 1948 Plasma inorganic iodide as a homeostatic regulator of thyroid function J Biol Chem 174 555 64 18865621
  34. [38]Braverman LE Ingbar SH 1963 Changes in thyroidal function during adaptation to large doses of iodide J Clin Investig 42 1216 31 14057854 PMC289393
  35. [39]Leoni SG Kimura ET Santisteban P De la Vieja A 2011 Regulation of thyroid oxidative state by thioredoxin reductase has a crucial role in thyroid responses to iodide excess Mol Endocrinol 25 1924 35 21903721 PMC5417175
  36. [40]Serrano-Nascimento C Calil-Silveira J Nunes MT 2010 Posttranscriptional regulation of sodium-iodide symporter mRNA expression in the rat thyroid gland by acute iodide administration Am J Physiol Cell Physiol 298 C893 99 20107044
  37. [41]Vono-Toniolo J Kopp P 2004 Thyroglobulin gene mutations and other genetic defects associated with congenital hypothyroidism Arq Bras Endocrinol Metabol 48 70 82 15611820
  38. [42]Stratford AL Boelaert K Tannahill LA Kim DS Warfield A 2005 Pituitary tumor transforming gene binding factor: a novel transforming gene in thyroid tumorigenesis J Clin Endocrinol Metab 90 4341 49 15886233
  39. [43]Boelaert K Smith VE Stratford AL Kogai T Tannahill LA 2007 PTTG and PBF repress the human sodium iodide symporter Oncogene 26 4344 56 17297475
  40. [44]Lacoste C Hervé J Bou Nader M Dos Santos A Moniaux N 2012 Iodide transporter NIS regulates cancer cell motility and invasiveness by interacting with the Rho guanine nucleotide exchange factor LARG Cancer Res 72 5505 15 22962269
  41. [45]Roepke TK King EC Reyna-Neyra A Paroder M Purtell K 2009 Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis Nat Med 15 1186 94 19767733 PMC2790327
  42. [46]Purtell K Paroder-Belenitsky M Reyna-Neyra A Nicola JP Koba W 2012 The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I− uptake FASEB J 26 3252 59 22549510 PMC3405278
  43. [47]Abbott GW Tai KK Neverisky DL Hansler A Hu Z 2014 KCNQ1, KCNE2, and Na+-coupled solute transporters form reciprocally regulating complexes that affect neuronal excitability Sci Signal 7 ra22 24595108 PMC4063528
  44. [48]Abbott GW 2015 The KCNE2 K+ channel regulatory subunit: ubiquitous influence, complex pathobiology Gene 569 162 72 26123744 PMC4917011
  45. [49]Di Cosmo C Fanelli G Tonacchera M Ferrarini E Dimida A 2006 The sodium-iodide symporter expression in placental tissue at different gestational age: an immunohistochemical study Clin Endocrinol 65 544 48 16984250
  46. [50]Mitchell AM Manley SW Morris JC Powell KA Bergert ER Mortimer RH 2001 Sodium iodide symporter (NIS) gene expression in human placenta Placenta 22 256 58 11170832
  47. [51]Morgenstern KE Vadysirisack DD Zhang Z Cahill KV Foster JA 2005 Expression of sodium iodide symporter in the lacrimal drainage system: implication for the mechanism underlying nasolacrimal duct obstruction in I131-treated patients Ophthalmic Plast Reconstr Surg 21 337 44 16234694
  48. [52]Riesco-Eizaguirre G Leoni SG Mendiola M Estevez-Cebrero MA Gallego MI 2014 NIS mediates iodide uptake in the female reproductive tract and is a poor prognostic factor in ovarian cancer J Clin Endocrinol Metab 99 E1199 208 24708099
  49. [53]Spitzweg C Dutton CM Castro MR Bergert ER Goellner JR 2001 Expression of the sodium iodide symporter in human kidney Kidney Int 59 1013 23 11231356
  50. [54]Marti-Climent JM Collantes M Jauregui-Osoro M Quincoces G Prieto E 2015 Radiation dosimetry and biodistribution in non-human primates of the sodium/iodide PET ligand [18F]-tetrafluoroborate EJNMMI Res 5 70 26635227 PMC4669333
  51. [55]Akturk M Oruc AS Danisman N Erkek S Buyukkagnici U 2013 Na+/I− symporter and type 3 iodothyronine deiodinase gene expression in amniotic membrane and placenta and its relationship to maternal thyroid hormones Biol Trace Element Res 154 338 44 23857380
  52. [56]Altorjay A Dohán O Szilágyi A Paroder M Wapnir IL Carrasco N 2007 Expression of the Na+/I− symporter (NIS) is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus BMC Cancer 7 5 17214887 PMC1794416
  53. [57]La Perle KM Kim DC Hall NC Bobbey A Shen DH 2013 Modulation of sodium/iodide symporter expression in the salivary gland Thyroid 23 1029 36 23441638 PMC3752512
  54. [58]Spitzweg C Joba W Morris JC Heufelder AE 1999 Regulation of sodium iodide symporter gene expression in FRTL-5 rat thyroid cells Thyroid 9 821 30 10482376
  55. [59]Dagogo-Jack S 1994 Dietary iodine affects epidermal growth factor levels in mouse thyroid and sub-maxillary glands Endocr Res 20 247 57 7995255
  56. [60]Geiszt M Witta J Baffi J Lekstrom K Leto TL 2003 Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense FASEB J 17 1502 4 12824283
  57. [61]Gupta A Lakhoo K Pritchard N Herbert M 2008 Epidermal growth factor in neonatal saliva Eur J Pediatr Surg 18 245 48 18629765
  58. [62]Venturi S Venturi M 2009 Iodine in evolution of salivary glands and in oral health Nutr Health 20 119 34 19835108
  59. [63]Nicola JP Basquin C Portulano C Reyna-Neyra A Paroder M Carrasco N 2009 The Na+/I− symporter mediates active iodide uptake in the intestine Am J Physiol Cell Physiol 296 C654 62 19052257 PMC2670652
  60. [64]Nicola JP Carrasco N Masini-Repiso AM 2015 Dietary I− absorption: expression and regulation of the Na+/I− symporter in the intestine Vitam Horm 98 1 31 25817864
  61. [65]Vejbjerg P Knudsen N Perrild H Laurberg P Andersen S 2009 Estimation of iodine intake from various urinary iodine measurements in population studies Thyroid 19 1281 86 19888863
  62. [66]Scott DA Wang R Kreman TM Sheffield VC Karniski LP 1999 The Pendred syndrome gene encodes a chloride-iodide transport protein Nat Genet 21 440 43 10192399
  63. [67]van den Hove MF Croizet-Berger K Jouret F Guggino SE Guggino WB 2006 The loss of the chloride channel, ClC-5, delays apical iodide efflux and induces a euthyroid goiter in the mouse thyroid gland Endocrinology 147 1287 96 16306076
  64. [68]Calebiro D Porazzi P Bonomi M Lisi S Grindati A 2011 Absence of primary hypothyroidism and goiter in Slc26a4 (−/−) mice fed on a low iodine diet J Endocrinol Investig 34 593 98 20834201
  65. [69]Iwata T Yoshida T Teranishi M Murata Y Hayashi Y 2011 Influence of dietary iodine deficiency on the thyroid gland in Slc26a4-null mutant mice Thyroid Res 4 10 21689387 PMC3141755
  66. [70]Cho JY Xing S Liu X Buckwalter TL Hwa L 2000 Expression and activity of human Na+/I− symporter in human glioma cells by adenovirus-mediated gene delivery Gene Ther 7 740 49 10822300
  67. [71]Renier C Vogel H Offor O Yao C Wapnir I 2010 Breast cancer brain metastases express the sodium iodide symporter J Neurooncol 96 331 36 19618116
  68. [72]Wapnir IL Goris M Yudd A Dohán O Adelman D 2004 The Na+/I− symporter mediates iodide uptake in breast cancer metastases and can be selectively down-regulated in the thyroid Clin Cancer Res 10 4294 302 15240514
  69. [73]Kogai T Curcio F Hyman S Cornford EM Brent GA Hershman JM 2000 Induction of follicle formation in long-term cultured normal human thyroid cells treated with thyrotropin stimulates iodide uptake but not sodium/iodide symporter messenger RNA and protein expression J Endocrinol 167 125 35 11018760
  70. [74]Kogai T Brent GA 2012 The sodium iodide symporter (NIS): regulation and approaches to targeting for cancer therapeutics Pharmacol Ther 135 355 70 22750642 PMC3408573
  71. [75]Kogai T Kanamoto Y Li AI Che LH Ohashi E 2005 Differential regulation of sodium/iodide symporter gene expression by nuclear receptor ligands in MCF-7 breast cancer cells Endocrinology 146 3059 69 15817668
  72. [76]Unterholzner S Willhauck MJ Cengic N Schütz M Göke B 2006 Dexamethasone stimulation of retinoic acid-induced sodium iodide symporter expression and cytotoxicity of 131-I in breast cancer cells J Clin Endocrinol Metab 91 69 78 16234306
  73. [77]Dohán O De la Vieja A Carrasco N 2006 Hydrocortisone and purinergic signaling stimulate sodium/iodide symporter (NIS)-mediated iodide transport in breast cancer cells Mol Endocrinol 20 1121 37 16439463
  74. [78]Kogai T Kanamoto Y Che LH Taki K Moatamed F 2004 Systemic retinoic acid treatment induces sodium/iodide symporter expression and radioiodide uptake in mouse breast cancer models Cancer Res 64 415 22 14729653
  75. [79]Brown-Grant K 1965 The metabolism of iodide by the thyroid gland and by the uterus during early pregnancy in the rat J Physiol 176 73 90 14281408 PMC1357158
  76. [80]Trovato M Vitarelli E Tripepi M Abate A Rizzo P 2008 Expression of NA-1 symporter (NIS) in endometrial mucosa of fertile, sterile and post-menopausal women Histol Histopathol 23 549 54 18283639
  77. [81]Lacroix L Mian C Caillou B Talbot M Filetti S 2001 Na+/I− symporter and Pendred syndrome gene and protein expressions in human extra-thyroidal tissues Eur J Endocrinol 144 297 302 11248751
  78. [82]Spitzweg C Joba W Eisenmenger W Heufelder AE 1998 Analysis of human sodium iodide symporter gene expression in extrathyroidal tissues and cloning of its complementary deoxyribonucleic acids from salivary gland, mammary gland, and gastric mucosa J Clin Endocrinol Metab 83 1746 51 9589686
  79. [83]Chaffin CL Vandevoort CA 2013 Follicle growth, ovulation, and luteal formation in primates and rodents: a comparative perspective Exp Biol Med 238 539 48 23856905
  80. [84]Am. Acad. Pediatr. Rose SR Am. Thyroid Assoc. Brown RS Lawson Wilkins Pediatr. Endocr. Soc. 2006 Update of newborn screening and therapy for congenital hypothyroidism Pediatrics 117 2290 303 16740880
  81. [85]Park SM Chatterjee VK 2005 Genetics of congenital hypothyroidism J Med Genet 42 379 89 15863666 PMC1736062
  82. [86]Clifton-Bligh RJ Wentworth JM Heinz P Crisp MS John R 1998 Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia Nat Genet 19 399 401 9697705
  83. [87]Dentice M Cordeddu V Rosica A Ferrara AM Santarpia L 2006 Missense mutation in the transcription factor NKX2-5: a novel molecular event in the pathogenesis of thyroid dysgenesis J Clin Endocrinol Metab 91 1428 33 16418214
  84. [88]Krude H Schutz B Biebermann H von Moers A Schnabel D 2002 Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency J Clin Investig 109 475 80 11854319 PMC150790
  85. [89]Macchia PE Lapi P Krude H Pirro MT Missero C 1998 PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis Nat Genet 19 83 86 9590296
  86. [90]Pohlenz J Dumitrescu A Zundel D Martiné U Schönberger W 2002 Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice J Clin Investig 109 469 73 11854318 PMC150877
  87. [91]Avbelj M Tahirovic H Debeljak M Kusekova M Toromanovic A 2007 High prevalence of thyroid peroxidase gene mutations in patients with thyroid dyshormonogenesis Eur J Endocrinol 156 511 19 17468186
  88. [92]Bizhanova A Kopp P 2010 Genetics and phenomics of Pendred syndrome Mol Cell Endocrinol 322 83 90 20298745
  89. [93]Gutnisky VJ Moya CM Rivolta CM Domené S Varela V 2004 Two distinct compound heterozygous constellations (R277X/IVS34-1G>C and R277X/R1511X) in the thyroglobulin (TG) gene in affected individuals of a Brazilian kindred with congenital goiter and defective TG synthesis J Clin Endocrinol Metab 89 646 57 14764776
  90. [94]Moreno JC Bikker H Kempers MJ van Trotsenburg AS Baas F 2002 Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism N Engl J Med 347 95 102 12110737
  91. [95]Moreno JC Klootwijk W van Toor H Pinto G D’Alessandro M 2008 Mutations in the iodotyrosine deiodinase gene and hypothyroidism N Engl J Med 358 1811 18 18434651
  92. [96]Pohlenz J Refetoff S 1999 Mutations in the sodium/iodide symporter (NIS) gene as a cause for iodide transport defects and congenital hypothyroidism Biochimie 81 469 76 10403177
  93. [97]Reed-Tsur MD De la Vieja A Ginter CS Carrasco N 2008 Molecular characterization of V59E NIS, a Na+/I− symporter mutant that causes congenital I- transport defect Endocrinology 149 3077 84 18339708 PMC2408800
  94. [98]Paroder V Nicola JP Ginter CS Carrasco N 2013 The iodide-transport-defect-causing mutation R124H: a delta-amino group at position 124 is critical for maturation and trafficking of the Na+/I− symporter J Cell Sci 126 3305 13 23690546 PMC3730242
  95. [99]Kosugi S Okamoto H Tamada A Sanchez-Franco F 2002 A novel peculiar mutation in the sodium/iodide symporter gene in Spanish siblings with iodide transport defect J Clin Endocrinol Metab 87 3830 36 12161518
  96. [100]De La Vieja A Ginter CS Carrasco N 2004 The Q267E mutation in the sodium/iodide symporter (NIS) causes congenital iodide transport defect (ITD) by decreasing the NIS turnover number J Cell Sci 117 677 87 14734652
  97. [101]Nicola JP Reyna-Neyra A Saenger P Rodriguez-Buritica DF Godoy JD 2015 The sodium/iodide symporter mutant V270E causes stunted growth but no cognitive deficiency J Clin Endocrinol Metab 100 E1353 61 26204134 PMC4596044
  98. [102]Montanelli L Agretti P Marco G Bagattini B Ceccarelli C 2009 Congenital hypothyroidism and late-onset goiter: identification and characterization of a novel mutation in the sodium/iodide symporter of the proband and family members Thyroid 19 1419 25 19916865
  99. [103]De la Vieja A Reed MD Ginter CS Carrasco N 2007 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 282 25290 98 17606623
  100. [104]Levy O Ginter CS De la Vieja A Levy D Carrasco N 1998 Identification of a structural requirement for thyroid Na+/I− symporter (NIS) function from analysis of a mutation that causes human congenital hypothyroidism FEBS Lett 429 36 40 9657379
  101. [105]Dohán O Gavrielides MV Ginter C Amzel LM Carrasco N 2002 Na+/I− symporter activity requires a small and uncharged amino acid residue at position 395 Mol Endocrinol 16 1893 902 12145342
  102. [106]Li W Nicola JP Amzel LM Carrasco N 2013 Asn441 plays a key role in folding and function of the Na+/I− symporter (NIS) FASEB J 27 3229 38 23650190 PMC3714583
  103. [107]De la Vieja A Ginter CS Carrasco N 2005 Molecular analysis of a congenital iodide transport defect: G543E impairs maturation and trafficking of the Na+/I− symporter Mol Endocrinol 19 2847 58 15976004
  104. [108]Portulano C Paroder-Belenitsky M Carrasco N 2014 The Na+/I− symporter (NIS): mechanism and medical impact Endocr Rev 35 106 49 24311738 PMC3895864
  105. [109]Nicola JP Nazar M Serrano-Nascimento C Goulart-Silva F Sobrero G 2011 Iodide transport defect: functional characterization of a novel mutation in the Na+/I− symporter 5′-untranslated region in a patient with congenital hypothyroidism J Clin Endocrinol Metab 96 E1100 7 21565787
  106. [110]Yamashita A Singh SK Kawate T Jin Y Gouaux E 2005 Crystal structure of a bacterial homologue of Na+/Cl−-dependent neurotransmitter transporters Nature 437 215 23 16041361
  107. [111]Khafizov K Perez C Koshy C Quick M Fendler K 2012 Investigation of the sodium-binding sites in the sodium-coupled betaine transporter BetP PNAS 109 E3035 44 23047697 PMC3497817
  108. [112]Weyand S Shimamura T Yajima S Suzuki S Mirza O 2008 Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter Science 322 709 13 18927357 PMC2885439
  109. [113]Ravera S Quick M Nicola JP Carrasco N Amzel LM 2015 Beyond non-integer Hill coefficients: a novel approach to analyzing binding data, applied to Na+-driven transporters J Gen Physiol 145 555 63 26009546 PMC4442788
  110. [114]Zhao C Stolzenberg S Gracia L Weinstein H Noskov S Shi L 2012 Ion-controlled conformational dynamics in the outward-open transition from an occluded state of LeuT Biophys J 103 878 88 23009837 PMC3433624
  111. [115]Loo DD Jiang X Gorraitz E Hirayama BA Wright EM 2013 Functional identification and characterization of sodium binding sites in Na symporters PNAS 110 E4557 66 24191006 PMC3839715
  112. [116]Meinild AK Forster IC 2012 Using lithium to probe sequential cation interactions with GAT1 Am J Physiol Cell Physiol 302 C1661 75 22460712
  113. [117]Paroder V Nicola JP Ginter CS Carrasco N 2013 The iodide transport defect-causing mutation R124H: a delta-amino group at position 124 is critical for maturation and trafficking of the Na+/I− symporter (NIS) J Cell Sci 126 3305 13 23690546 PMC3730242
  114. [118]Shimura H Haraguchi K Miyazaki A Endo T Onaya T 1997 Iodide uptake and experimental 131I therapy in transplanted undifferentiated thyroid cancer cells expressing the Na+/I− symporter gene Endocrinology 138 4493 96 9322970
  115. [119]Baril P Martin-Duque P Vassaux G 2010 Visualization of gene expression in the live subject using the Na/I symporter as a reporter gene: applications in biotherapy Br J Pharmacol 159 761 71 19814733 PMC2829202
  116. [120]Boland A Ricard M Opolon P Bidart JM Yeh P 2000 Adenovirus-mediated transfer of the thyroid sodium/iodide symporter gene into tumors for a targeted radiotherapy Cancer Res 60 3484 92 10910060
  117. [121]Penheiter AR Russell SJ Carlson SK 2012 The sodium iodide symporter (NIS) as an imaging reporter for gene, viral, and cell-based therapies Curr Gene Ther 12 33 47 22263922 PMC3367315
  118. [122]Spitzweg C Dietz AB O’Connor MK Bergert ER Tindall DJ 2001 In vivo sodium iodide symporter gene therapy of prostate cancer Gene Ther 8 1524 31 11704812
  119. [123]Spitzweg C Heufelder AE Morris JC 2000 Thyroid iodine transport Thyroid 10 321 30 10807060
  120. [124]Hingorani M Spitzweg C Vassaux G Newbold K Melcher A 2010 The biology of the sodium iodide symporter and its potential for targeted gene delivery Curr Cancer Drug Targets 10 242 67 20201784 PMC3916908
  121. [125]Spitzweg C Morris JC 2004 Gene therapy for thyroid cancer: current status and future prospects Thyroid 14 424 34 15242569
  122. [126]Niu G Gaut AW Ponto LL Hichwa RD Madsen MT 2004 Multimodality noninvasive imaging of gene transfer using the human sodium iodide symporter J Nucl Med 45 445 49 15001685
  123. [127]Msaouel P Iankov ID Allen C Aderca I Federspiel MJ 2009 Noninvasive imaging and radiovirotherapy of prostate cancer using an oncolytic measles virus expressing the sodium iodide symporter Mol Ther 17 2041 48 19773744 PMC2810133
  124. [128]Peerlinck I Merron A Baril P Conchon S Martin-Duque P 2009 Targeted radionuclide therapy using a Wnt-targeted replicating adenovirus encoding the Na/I symporter Clin Cancer Res 15 6595 601 19861465
  125. [129]Haddad D Zanzonico PB Carlin S Chen CH Chen NG 2012 A vaccinia virus encoding the human sodium iodide symporter facilitates long-term image monitoring of virotherapy and targeted radiotherapy of pancreatic cancer J Nucl Med 53 1933 42 23139088 PMC6386167
  126. [130]Russell SJ Federspiel MJ Peng KW Tong C Dingli D 2014 Remission of disseminated cancer after systemic oncolytic virotherapy Mayo Clin Proc 89 926 33 24835528 PMC4225126
  127. [131]Li H Peng KW Dingli D Kratzke RA Russell SJ 2010 Oncolytic measles viruses encoding interferon beta and the thyroidal sodium iodide symporter gene for mesothelioma virotherapy Cancer Gene Ther 17 550 58 20379224 PMC2907639
  128. [132]Dwyer RM Bergert ER O’Connor MK Gendler SJ Morris JC 2005 In vivo radioiodide imaging and treatment of breast cancer xenografts after MUC1-driven expression of the sodium iodide symporter Clin Cancer Res 11 1483 89 15746050
  129. [133]Dwyer RM Bergert ER O’Connor MK Gendler SJ Morris JC 2006 Adenovirus-mediated and targeted expression of the sodium-iodide symporter permits in vivo radioiodide imaging and therapy of pancreatic tumors Hum Gene Ther 17 661 68 16776574
  130. [134]Dwyer RM Bergert ER O’Connor MK Gendler SJ Morris JC 2006 Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice Gene Ther 13 60 66 16121204
  131. [135]Dwyer RM Schatz SM Bergert ER Myers RM Harvey ME 2005 A preclinical large animal model of adenovirus-mediated expression of the sodium-iodide symporter for radioiodide imaging and therapy of locally recurrent prostate cancer Mol Ther 12 835 41 16054438
  132. [136]Trujillo MA Oneal MJ Davydova J Bergert E Yamamoto M Morris JC 3rd 2009 Construction of an MUC-1 promoter driven, conditionally replicating adenovirus that expresses the sodium iodide symporter for gene therapy of breast cancer Breast Cancer Res 11 R53 19635153 PMC2750114
  133. [137]Trujillo MA Oneal MJ McDonough S Qin R Morris JC 2010 A probasin promoter, conditionally replicating adenovirus that expresses the sodium iodide symporter (NIS) for radiovirotherapy of prostate cancer Gene Ther 17 1325 32 20428214 PMC2914818
  134. [138]Naik S Russell SJ 2009 Engineering oncolytic viruses to exploit tumor specific defects in innate immune signaling pathways Expert Opin Biol Ther 9 1163 76 19637971
  135. [139]Peng KW Ahmann GJ Pham L Greipp PR Cattaneo R Russell SJ 2001 Systemic therapy of myeloma xenografts by an attenuated measles virus Blood 98 2002 7 11567982
  136. [140]Galanis E Atherton PJ Maurer MJ Knutson KL Dowdy SC 2015 Oncolytic measles virus expressing the sodium iodide symporter to treat drug-resistant ovarian cancer Cancer Res 75 22 30 25398436 PMC4377302
  137. [141]Blechacz B Splinter PL Greiner S Myers R Peng KW 2006 Engineered measles virus as a novel oncolytic viral therapy system for hepatocellular carcinoma Hepatology 44 1465 77 17133484
  138. [142]Domingo-Musibay E Allen C Kurokawa C Hardcastle JJ Aderca I 2014 Measles Edmonston vaccine strain derivatives have potent oncolytic activity against osteosarcoma Cancer Gene Ther 21 483 90 25394505 PMC4337839
  139. [143]Li H Peng KW Russell SJ 2012 Oncolytic measles virus encoding thyroidal sodium iodide symporter for squamous cell cancer of the head and neck radiovirotherapy Hum Gene Ther 23 295 301 22235810 PMC3300082
  140. [144]Liu YP Wang J Avanzato VA Bakkum-Gamez JN Russell SJ 2014 Oncolytic vaccinia virotherapy for endometrial cancer Gynecol Oncol 132 722 29 24434058 PMC3977925
  141. [145]Haddad D Chen CH Carlin S Silberhumer G Chen NG 2012 Imaging characteristics, tissue distribution, and spread of a novel oncolytic vaccinia virus carrying the human sodium iodide symporter PLOS ONE 7 e41647 22912675 PMC3422353
  142. [146]Haddad D Chen NG Zhang Q Chen CH Yu YA 2011 Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus J Transl Med 9 36 21453532 PMC3080806
  143. [147]Belin LJ Ady JW Lewis C Marano D Gholami S 2013 An oncolytic vaccinia virus expressing the human sodium iodine symporter prolongs survival and facilitates SPECT/CT imaging in an orthotopic model of malignant pleural mesothelioma Surgery 154 486 95 23890748 PMC4123996
  144. [148]Jun KH Gholami S Song TJ Au J Haddad D 2014 A novel oncolytic viral therapy and imaging technique for gastric cancer using a genetically engineered vaccinia virus carrying the human sodium iodide symporter J Exp Clin Cancer Res 33 2 24383569 PMC3883485
  145. [149]Eveno C Mojica K Ady JW Thorek DL Longo V 2015 Gene therapy using therapeutic and diagnostic recombinant oncolytic vaccinia virus GLV-1h153 for management of colorectal peritoneal carcinomatosis Surgery 157 331 37 25616946 PMC4373422
  146. [150]Gholami S Chen CH Belin LJ Lou E Fujisawa S 2013 Vaccinia virus GLV-1h153 is a novel agent for detection and effective local control of positive surgical margins for breast cancer Breast Cancer Res 15 R26 23506710 PMC3672815
  147. [151]Gholami S Haddad D Chen CH Chen NG Zhang Q 2011 Novel therapy for anaplastic thyroid carcinoma cells using an oncolytic vaccinia virus carrying the human sodium iodide symporter Surgery 150 1040 47 22136819
  148. [152]Mansfield DC Kyula JN Rosenfelder N Chao-Chu J Kramer-Marek G 2016 Oncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer Gene Ther 23 357 68 26814609 PMC4827015
  149. [153]Lehner S Lang C Kaissis G Todica A Zacherl MJ 2015 124I-PET assessment of human sodium iodide symporter reporter gene activity for highly sensitive in vivo monitoring of teratoma formation in mice Mol Imaging Biol 17 874 83 25896817
  150. [154]Knoop K Schwenk N Schmohl K Müller A Zach C 2015 Mesenchymal stem cell-mediated, tumor stroma-targeted radioiodine therapy of metastatic colon cancer using the sodium iodide symporter as theranostic gene J Nucl Med 56 600 6 25745085
  151. [155]Park JW Jung KH Lee JH Moon SH Cho YS 2016 Imaging early fate of cancer stem cells in mouse hindlimbs with sodium iodide symporter gene and I-124 PET Mol Imaging Biol 18 748 26914278
  152. [156]Micci MA Boone DR Parsley MA Wei J Patrikeev I 2015 Development of a novel imaging system for cell therapy in the brain Stem Cell Res Ther 6 131 26194790 PMC4534109
  153. [157]Terrovitis J Kwok KF Lautamaki R Engles JM Barth AS 2008 Ectopic expression of the sodium-iodide symporter enables imaging of transplanted cardiac stem cells in vivo by single-photon emission computed tomography or positron emission tomography J Am Coll Cardiol 52 1652 60 18992656 PMC4980098
  154. [158]Templin C Zweigerdt R Schwanke K Olmer R Ghadri JR 2012 Transplantation and tracking of human-induced pluripotent stem cells in a pig model of myocardial infarction: assessment of cell survival, engraftment, and distribution by hybrid single photon emission computed tomography/computed tomography of sodium iodide symporter transgene expression Circulation 126 430 39 22767659
  155. [159]Lee AR Woo SK Kang SK Lee SY Lee MY 2015 Adenovirus-mediated expression of human sodium-iodide symporter gene permits in vivo tracking of adipose tissue-derived stem cells in a canine myocardial infarction model Nucl Med Biol 42 621 29 25899941
  156. [160]Shi S Zhang M Guo R Miao Y Zhang M 2014 Feasibility of lentiviral-mediated sodium iodide symporter gene delivery for the efficient monitoring of bone marrow-derived mesenchymal stem cell transplantation and survival Int J Mol Med 34 1547 54 25319483
  157. [161]Shi S Zhang M Guo R Miao Y Zhang X Li B 2015 Molecular imaging to monitor repair of myocardial infarction using genetically engineered bone marrow-derived mesenchymal stem cells Curr Gene Ther 15 460 71 25892408
  158. [162]Chang C Chan A Lin X Higuchi T Terrovitis J 2013 Cellular bioenergetics is an important determinant of the molecular imaging signal derived from luciferase and the sodium-iodide symporter Circ Res 112 441 50 23255420 PMC3863605
  159. [163]Kang JH Lee DS Paeng JC Lee JS Kim YH 2005 Development of a sodium/iodide symporter (NIS)-transgenic mouse for imaging of cardiomyocyte-specific reporter gene expression J Nucl Med 46 479 83 15750162
  160. [164]Hickey RD Mao SA Amiot B Suksanpaisan L Miller A 2015 Noninvasive 3-dimensional imaging of liver regeneration in a mouse model of hereditary tyrosinemia type 1 using the sodium iodide symporter gene Liver Transpl 21 442 53 25482651 PMC5957080
  161. [165]Holvoet B Quattrocelli M Belderbos S Pollaris L Wolfs E 2015 Sodium iodide symporter PET and BLI noninvasively reveal mesoangioblast survival in dystrophic mice Stem Cell Rep 5 1183 95 PMC4682284 26626179

Cited by

Sorted by citations

Authors
Ravera, S., Reyna-Neyra, A., Ferrandino, G., Amzel, L. M., & Carrasco, N.
Affiliations
  • Yale University (US)
  • Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut 06510;
  • Johns Hopkins University (US)
Corresponding author
  • Ravera, Silvia
  • Ferrandino, Giuseppe
ORCID
Venue
Annual Review of Physiology
Publisher
Annual Reviews
Published
2017-02-10
Volume
79
Issue
1
Pages
261-289
ISSN
  • 0066-4278 (ISSN-L)
  • 1545-1585
DOI
10.1146/annurev-physiol-022516-034125
PMC
PMC5739519
OpenAlex
W2467366089
Cited by
298
References
0
Citations by year
2026: 38 · 2025: 28 · 2024: 31 · 2023: 39 · 2022: 40 · 2021: 45 · 2020: 31 · 2019: 25 · 2018: 14 · 2017: 7
FWCI
3.06
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Annual Review of Physiology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM114250)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK041544)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Chemical Analysis and Environmental Impact
Keywords
sodium iodide symporter, iodide transport, thyroid hormone synthesis, radioiodine therapy, thyroid cancer, reporter genes, viral vectors, stem cells, thyroid imaging
MeSH terms
Sodium-Iodide Symporters, Animals, Humans, Iodides, Thyroid Gland, Thyroid Neoplasms, Genes, Reporter, Symporters

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review