Surprising substrate versatility in SLC5A6: Na+-coupled I- transport by the human Na+/multivitamin transporter (hSMVT).
Iodide (I(-)) is an essential constituent of the thyroid hormones triiodothyronine and thyroxine, which are required for the development of the central nervous system in the fetus and newborn. I(-) uptake in the thyroid is mediated by the Na(+)/I(-) symporter (NIS). NIS has gained particular medical interest due to its sensitivity to the environmental pollutant perchlorate (ClO(4)(-)) and its implication in radioiodide cancer treatment. Recently, others have shown that I(-) absorption in the intestine is mediated by NIS (Nicola, J. P., Basquin, C., Portulano, C., Reyna-Neyra, A., Paroder, M., and Carrasco, N. (2009) Am. J. Physiol. Cell Physiol. 296, C654-662). However, their data suggest the participation of other systems in the homeostasis of I(-), in particular because in vivo uptake studies revealed a ClO(4)(-)-insensitive transport component. Here, we describe Na(+)-coupled I(-) uptake by the human Na(+)/multivitamin transporter (hSMVT), a related protein isolated from the placenta, where it was suggested to supply the fetus with the water-soluble vitamins biotin and pantothenic acid, and α-lipoic acid. hSMVT-mediated Na(+)/I(-) symport is inhibited by the other three organic hSMVT substrates but not by NIS substrates; notably, hSMVT is insensitive to ClO(4)(-). Because hSMVT is found in the intestine and in many other tissues, we propose that hSMVT may play an important role in the homeostasis of I(-) in the body.
de Carvalho
Fernanda Delmondes
FD
Center for Molecular Recognition, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Quick
Matthias
M
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001710:Biotin / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D006801:Humans; D007454:Iodides / Q000378:metabolism* / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D010205:Pantothenic Acid / Q000378:metabolism / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D013379:Substrate Specificity; D027981:Symporters / Q000378:metabolism*; D008063:Thioctic Acid / Q000378:metabolism / Q000494:pharmacology; D014982:Xenopus laevis
D007454:Iodides; D027981:Symporters; C119981:biotin transporter; D010205:Pantothenic Acid; D001710:Biotin; D008063:Thioctic Acid; D012964:Sodium