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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
The sodium-iodide symporter (NIS) is an iodide transporter found principally in the thyroid gland where it mediates the accumulation of I- within thyrocytes. Transport of I- by NIS from the blood across the basolateral membrane followed by apical efflux into the colloidal lumen, mediated at least in part by pendrin (SLC22A4), and most likely not SMCT1 (SLC5A8) as once thought, provides the I- required for the synthesis of the thyroid hormones triiodothyronine (triiodothyronine) and thyroxine (T4) . NIS is also expressed in the salivary glands, gastric mucosa, intestinal enterocytes and lactating breast. NIS mediates I- absorption in the intestine and I- secretion into the milk. SMVT is expressed on the apical membrane of intestinal enterocytes and colonocytes and is the main system responsible for biotin (vitamin H) and pantothenic acid (vitamin B5) uptake in humans . SMVT located in kidney proximal tubule epithelial cells mediates the reabsorption of biotin and pantothenic acid. SMCT1 (SLC5A8), which transports a wide range of monocarboxylates, is expressed in the apical membrane of epithelia of the small intestine, colon, kidney, brain neurones and the retinal pigment epithelium . SMCT2 (SLC5A12) also localises to the apical membrane of kidney, intestine, and colon, but in the brain and retina is restricted to astrocytes and Müller cells, respectively . SMCT1 is a high-affinity transporter whereas SMCT2 is a low-affinity transporter. The physiological substrates for SMCT1 and SMCT2 are lactate (L-lactic acid and D-lactic acid), pyruvic acid, propanoic acid, and nicotinic acid in non-colonic tissues such as the kidney. SMCT1 is also likely to be the principal transporter for the absorption of nicotinic acid (vitamin B3) in the intestine and kidney . In the small intestine and colon, the physiological substrates for these transporters are nicotinic acid and the short-chain fatty acids acetic acid, propanoic acid, and butyric acid that are produced by bacterial fermentation of dietary fiber . In the kidney, SMCT2 is responsible for the bulk absorption of lactate because of its low-affinity/high-capacity nature. Absence of both transporters in the kidney leads to massive excretion of lactate in urine and consequently drastic decrease in the circulating levels of lactate in blood . SMCT1 also functions as a tumour suppressor in the colon as well as in various other non-colonic tissues . The tumour-suppressive function of SMCT1 is based on its ability to transport pyruvic acid, an inhibitor of histone deacetylases, into cells in non-colonic tissues ; in the colon, the ability of SMCT1 to transport butyric acid and propanoic acid, also inhibitors of histone deacetylases, underlies the tumour-suppressive function of this transporter [6-7,9]. The ability of SMCT1 to promote histone acetylase inhibition through accumulation of butyric acid and propanoic acid in immune cells is also responsible for suppression of dendritic cell development in the colon .
1. Bizhanova A, Kopp P. (2009) Minireview: The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid. Endocrinology, 150 (3): 1084-90. [PMID:19196800]
2. Coady MJ, Wallendorff B, Bourgeois F, Charron F, Lapointe JY. (2007) Establishing a definitive stoichiometry for the Na+/monocarboxylate cotransporter SMCT1. Biophys. J., 93 (7): 2325-31. [PMID:17526579]
3. de Carvalho FD, Quick M. (2011) Surprising substrate versatility in SLC5A6: Na+-coupled I- transport by the human Na+/multivitamin transporter (hSMVT). J. Biol. Chem., 286 (1): 131-7. [PMID:20980265]
4. 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. Proc. Natl. Acad. Sci. U.S.A., 104 (51): 20250-5. [PMID:18077370]
5. 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 (43): 27230-8. [PMID:9341168]
6. Ganapathy V, Thangaraju M, Gopal E, Martin PM, Itagaki S, Miyauchi S, Prasad PD. (2008) Sodium-coupled monocarboxylate transporters in normal tissues and in cancer. AAPS J, 10 (1): 193-9. [PMID:18446519]
7. Ganapathy V, Thangaraju M, Prasad PD. (2009) Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol. Ther., 121 (1): 29-40. [PMID:18992769]
8. Gopal E, Fei YJ, Miyauchi S, Zhuang L, Prasad PD, Ganapathy V. (2005) Sodium-coupled and electrogenic transport of B-complex vitamin nicotinic acid by slc5a8, a member of the Na/glucose co-transporter gene family. Biochem. J., 388 (Pt 1): 309-16. [PMID:15651982]
9. Gupta N, Martin PM, Prasad PD, Ganapathy V. (2006) SLC5A8 (SMCT1)-mediated transport of butyrate forms the basis for the tumor suppressive function of the transporter. Life Sci., 78 (21): 2419-25. [PMID:16375929]
10. Itagaki S, Gopal E, Zhuang L, Fei YJ, Miyauchi S, Prasad PD, Ganapathy V. (2006) Interaction of ibuprofen and other structurally related NSAIDs with the sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8). Pharm. Res., 23 (6): 1209-16. [PMID:16729224]
11. Miyauchi S, Gopal E, Fei YJ, Ganapathy V. (2004) Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids. J. Biol. Chem., 279 (14): 13293-6. [PMID:14966140]
12. Prasad PD, Srinivas SR, Wang H, Leibach FH, Devoe LD, Ganapathy V. (2000) Electrogenic nature of rat sodium-dependent multivitamin transport. Biochem. Biophys. Res. Commun., 270 (3): 836-40. [PMID:10772912]
13. Said HM. (2009) Cell and molecular aspects of human intestinal biotin absorption. J. Nutr., 139 (1): 158-62. [PMID:19056639]
14. Said HM, Redha R, Nylander W. (1989) Biotin transport in the human intestine: inhibition by anticonvulsant drugs. Am. J. Clin. Nutr., 49 (1): 127-31. [PMID:2911998]
15. Singh N, Thangaraju M, Prasad PD, Martin PM, Lambert NA, Boettger T, Offermanns S, Ganapathy V. (2010) Blockade of dendritic cell development by bacterial fermentation products butyrate and propionate through a transporter (Slc5a8)-dependent inhibition of histone deacetylases. J. Biol. Chem., 285 (36): 27601-8. [PMID:20601425]
16. Thangaraju M, Ananth S, Martin PM, Roon P, Smith SB, Sterneck E, Prasad PD, Ganapathy V. (2006) c/ebpdelta Null mouse as a model for the double knock-out of slc5a8 and slc5a12 in kidney. J. Biol. Chem., 281 (37): 26769-73. [PMID:16873376]
17. Thangaraju M, Gopal E, Martin PM, Ananth S, Smith SB, Prasad PD, Sterneck E, Ganapathy V. (2006) SLC5A8 triggers tumor cell apoptosis through pyruvate-dependent inhibition of histone deacetylases. Cancer Res., 66 (24): 11560-4. [PMID:17178845]
18. Wang H, Huang W, Fei YJ, Xia H, Yang-Feng TL, Leibach FH, Devoe LD, Ganapathy V, Prasad PD. (1999) Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. J. Biol. Chem., 274 (21): 14875-83. [PMID:10329687]
Database page citation:
Sodium iodide symporter, sodium-dependent multivitamin transporter and sodium-coupled monocarboxylate transporters. Accessed on 30/04/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=174.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Transporters. Br J Pharmacol. 172: 6110-6202.