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The Na⁺/I⁻ symporter (NIS) mediates electroneutral active transport of the environmental pollutant perchlorate

Dohán, Orsolya, Portulano, Carla, Basquin, Cécile, Reyna-Neyra, Andrea, Amzel, L. Mario, Carrasco, Nancy
Proceedings of the National Academy of Sciences of the United States of America 2007 v.104 no.51 pp. 20250-20255
active transport, biosynthesis, iodides, lactation, milk, models, neonates, perchlorates, plasma membrane, pollutants, public health, risk, sodium, stoichiometry, symporters, thyroid hormones, tissues, water pollution, United States
The Na+/I− symporter (NIS) is a key plasma membrane protein that mediates active I− uptake in the thyroid, lactating breast, and other tissues with an electrogenic stoichiometry of 2 Na+ per I−. In the thyroid, NIS-mediated I− uptake is the first step in the biosynthesis of the iodine-containing thyroid hormones, which are essential early in life for proper CNS development. In the lactating breast, NIS mediates the translocation of I− to the milk, thus supplying this essential anion to the nursing newborn. Perchlorate (ClO4 −) is a well known competitive inhibitor of NIS. Exposure to food and water contaminated with ClO4 − is common in the U.S. population, and the public health impact of such exposure is currently being debated. To date, it is still uncertain whether ClO4 − is a NIS blocker or a transported substrate of NIS. Here we show in vitro and in vivo that NIS actively transports ClO4 −, including ClO4 − translocation to the milk. A simple mathematical fluxes model accurately predicts the effect of ClO4 − transport on the rate and extent of I− accumulation. Strikingly, the Na+/ ClO4 − transport stoichiometry is electroneutral, uncovering that NIS translocates different substrates with different stoichiometries. That NIS actively concentrates ClO4 − in maternal milk suggests that exposure of newborns to high levels of ClO4 − may pose a greater health risk than previously acknowledged because ClO4 − would thus directly inhibit the newborns' thyroidal I− uptake.