Sodium Iodide Symporter

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Sodium Iodide Symporter
Properties of human protein
Mass / length primary structure 643 amino acids
Secondary to quaternary structure multipass membrane protein
Identifier
Gene names SLC5A5  ; NIS
External IDs
Transporter classification
TCDB 2.A.21.5.1
designation Solut: Sodium Symporter Family
Occurrence
Homology family Sodium Solute Symporter
Parent taxon Creature
Exceptions plants

The sodium iodide symporter ( NIS ), also known as sodium iodide cotransporter , is a protein in the cell membrane that catalyzes the smuggling of iodide ions from the blood into the cell . So it is a transport protein . NIS occurs in all living things except plants. In humans, NIS is mainly produced in thyroid follicle cells , but also to a lesser extent in the mammary glands and ovaries . Mutations in the SLC5A5 - gene can NIS deficiency and this to hypothyroidism ( Dyshormogene Struma result).

The membrane transport equation is:

Solute (outside) + 2 Na + (outside) ⇒ Solute (inside) + 2 Na + (inside)

Monovalent anions with an ion volume similar to that of iodide (about 4 × 10 −23 cm 3 ) compete with the iodide at the sodium iodide symporter. In addition to iodide, the anions bromide , chlorate , bromate , periodate , perchlorate , thiocyanate , selenocyanate , nitrate and tetrafluoroborate can function as solutes in NIS . The iodide concentration in the cell can be 30 to 40 times higher than in the plasma.

The human protein consists of 13 transmembrane domains with 643 amino acids and a molecular mass of 68,666  Da .

regulation

NIS production is increased by inhibiting the PI3K signaling pathway , but also by radiation. Membrane transport through NIS can be stimulated with thyrotropin ; The transport is inhibited by high iodide concentrations in the cell, but also, for example, by perchlorate ion, which has a 30 times higher affinity for NIS than iodide. The apical forwarding into the colloidal space takes place via the Pendrin transporter .

Nuclear medicine application

Due to the ability to absorb technetium or radioactive iodine, SLC5A5 is used in nuclear medicine as a reporter gene to document the localization, functionality and treatability of (possibly malignant degenerate) thyroid cells in vivo ; With suitable radionuclides (e.g. 131 I , as beta emitters) it also enables therapy. Other radioisotopes that are also carried by NIS, such as 211 At , could improve cancer therapy.

Individual evidence

  1. ↑ UniProt entry
  2. ↑ a b T. Kuwert. Thyroid. In: T. Kuwert, F. Grünwald, U. Haberkorn, T. Krause: Nuclear medicine. Stuttgart, New York 2008, ISBN 978-3-13-118504-4 .
  3. ↑ TCDB : 2.A.21
  4. ↑ Jassal / D'Eustachio / reactome.org: Iodide is taken up by thyroid epithelial cells  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.@1@ 2Template: dead link / reactome.org  
  5. ↑ Kogai T, Sajid-Crockett S, Newmarch LS, Liu YY, Brent GA: Phosphoinositide-3-kinase inhibition induces sodium / iodide symporter expression in rat thyroid cells and human papillary thyroid cancer cells . In: J. Endocrinol. . 199, No. 2, November 2008, pp. 243-52. doi : 10.1677 / JOE-08-0333 . PMID 18762555 .
  6. ↑ Hingorani M, White CL, Zaidi S, et al : Radiation-mediated up-regulation of gene expression from replication-defective adenoviral vectors: implications for sodium iodide symporter gene therapy . In: Clin. Cancer Res . 14, No. 15, August 2008, pp. 4915-24. doi : 10.1158 / 1078-0432.CCR-07-4049 . PMID 18676766 .
  7. ^ Tran N, Valentín-Blasini L, Blount BC, et al : Thyroid-stimulating hormone increases active transport of perchlorate into thyroid cells . In: Am. J. Physiol. Endocrinol. Metab. . 294, No. 4, April 2008, pp. E802-6. doi : 10.1152 / ajpendo.00013.2008 . PMID 18303123 .
  8. ↑ Löffler / Petridas: Biochemistry and Pathobiochemistry . 9th edition. Springer-Verlag, Berlin 2014, ISBN 978-3-642-17972-3 , pp. 516 .
  9. ↑ Terrovitis J, Kwok KF, Lautamäki R, et al : 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 . In: J. Am. Coll. Cardiol. . 52, No. 20, November 2008, pp. 1652-60. doi : 10.1016 / j.jacc.2008.06.051 . PMID 18992656 .
  10. ↑ Dadachova E, N Carrasco: The Na / I symporter (NIS): imaging and therapeutic applications . In: Semin Nucl Med . 34, No. 1, January 2004, pp. 23-31. PMID 14735456 .
  11. ↑ Willhauck MJ, Samani BR, Wolf I, et al : The potential of 211Astatine for NIS-mediated radionuclide therapy in prostate cancer . In: Eur. J. Nucl. Med. Mol. Imaging . 35, No. 7, July 2008, pp. 1272-81. doi : 10.1007 / s00259-008-0775-4 . PMID 18404268 .

Web links

Wikibooks: Sodium Iodide Symporter  - Learning and teaching materials