Surprising Substrate Versatility in SLC5A6

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 (ClO4−) 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 ClO4−-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 ClO4−. 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.