SLC5A5 Membrane Protein Introduction

Introduction of SLC5A5

SLC5A5 (solute carrier family 5 member 4) also known as NIS or TDH1 is an intrinsic membrane protein of approximately 68.7 kDa. It is a member of the superfamily of sodium/solute symporters and consists of 13 transmembrane helices and 643 amino acid residues. In humans, this protein is encoded by the SLC5A5 gene localized at the chromosome 19p13.11. SLC5A5 has 13 transmembrane domains, a cytosolic C-terminal, an extracellular N-terminal, and 3 N-linked glycosylation sites. It is primarily found in the thyroid gland, a butterfly-shaped organ in the lower neck, and mediates active I(-) transport in the thyroid and other tissues involving salivary glands, stomach, small intestine, lactating breast, placenta, and testis.

Function of SLC5A5 Membrane Protein

SLC5A5 is a plasma membrane glycoprotein that participates in the efficient iodide uptake from the bloodstream into thyroid follicular cells. In the thyroid, SLC5A5-mediated uptake is an important process of iodide organification and plays a key role in the first step in the biosynthesis of the thyroid hormones (e.g. triiodothyronine, thyroxine) of which iodine is a critical component. These hormones are essential for the development of central nervous systems and the lungs in the newborn and for intermediary metabolism at all ages. SLC5A5 is an ion pump that actively transports iodide by the sodium gradient generated by Na(+)/K(+)-ATPase. Biophysically, it transports Na(-): I(−) at a ratio of 2:1 and thus is electrogenic. This transporter makes a significant contribution to the iodine metabolism and thyroid regulation and therefore, to the control of human metabolism in general. The expression of SLC5A5 is finely modulated at transcriptional and post-transcriptional levels. And its function has been widely exploited in the diagnosis and treatment of related benign and malignant thyroid diseases.

Fig.1 NIS homology model. (Portulano, 2014)

Application of SLC5A5 Membrane Protein in Literature

1. Suh S., et al. mRNA expression of SLC5A5 and SLC2A family genes in papillary thyroid cancer: an analysis of the cancer genome atlas. Yonsei Med J. 2018, 59(6): 746-753. PubMed ID: 29978611
   
   

   The expression of SLC5A5 mRNA was found negatively associated with SLC2A1 mRNA. The result provided a molecular basis for the management of papillary thyroid cancer (PTC) with negative whole-body radioactive iodine scans (WBS). Additionally, a higher expression of SLC5A5 mRNA was correlated with less PTC recurrence, but not with deaths.

2. Soler Arias E.A., et al. Congenital dyshormonogenic hypothyroidism with goiter caused by a sodium/iodide symporter (SLC5A5) mutation in a family of Shih-Tzu dogs. Domest Anim Endocrinol. 2018, 65: 1-8. PubMed ID: 29777899
   
   

   An iodide transport defect in the thyroid gland was believed to lead to the congenital dyshormonogenic hypothyroidism with goiter (CDHG) in two members of a family of Shih-Tzu dogs. Both dogs, remarkably, were also diagnosed with dilated cardiomyopathy at 24 and 1.5 mo of age. These findings were the first proof of a SLC5A5 mutation in dogs and presented a novel genetic cause of CDHG.

3. Watanabe Y., et al. A novel missense mutation in the SLC5A5 gene in a sudanese family with congenital hypothyroidism. Thyroid. 2018. PubMed ID: 29759035
   
   

   This study identified a novel homozygous missense mutation in the SLC5A5 gene from a Sudanese family with congenital hypothyroidism (CH). The mutation was localized at the transmembrane segments (TMS) IX of the sodium-iodide symporter (NIS) protein, which was important for sodium-iodide symporter (NIS) function.

4. Tavares C., et al. mTOR pathway in papillary thyroid carcinoma: different contributions of mTORC1 and mTORC2 complexes for tumor behavior and SLC5A5 mRNA expression. Int J Mol Sci. 2018, 19(5). PubMed ID: 29757257
   
   

   Authors manifested that phospho-mTOR expression was correlated with tumor aggressiveness, therapy resistance, as well as lower mRNA expression of SLC5A5 in papillary thyroid carcinoma, while phospho-S6 level was correlated with less aggressive clinicopathological features.

5. Yaglova N.V., et al. Sex differences in the production of SLC5A5, thyroid peroxidase, and thyroid hormones in pubertal rats exposed to endocrine disruptor dichlorodiphenyltrichloroethane (DDT) during postnatal ontogeny. Bull Exp Biol Med. 2018, 164(4): 430-433. PubMed ID: 29500802
   
   

   Sex differences in the expression of SLC5A5 and thyroid peroxidase were evaluated in pubertal rats which are exposed to endocrine disruptor dichlorodiphenyltrichloroethane (DDT) from the first postnatal day. It was found that exposure to DDT reduced the SLC5A5 expression in peripheral regions of thyroid lobes in males and in central regions in females.

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Reference

1. Portulano C, et al. (2014). The Na⁺/I^- symporter (NIS): mechanism and medical impact. Endocr Rev. 35(1), 106-149.

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