Open AccessThe Na + /I − symporter (NIS) mediates electroneutral active transport of the environmental pollutant perchlorate
Author(s) -
Orsolya Dohán,
Carla Portulano,
Cécile Basquin,
Andrea Reyna-Neyra,
L. Mario Amzel,
Nancy Carrasco
Publication year - 2007
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0707207104
Subject(s) - symporter , chemistry , perchlorate , population , thyroid , iodine , membrane transport , medicine , biochemistry , endocrinology , transporter , membrane , biology , ion , environmental health , organic chemistry , gene
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 showin vitro andin 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.