Publications

• Thyroid Na+/I- symporter. Mechanism, stoichiometry, and specificity.

  Eskandari S., Loo D.D., Dai G., Levy O., Wright E.M., Carrasco N.

  The rat thyroid Na+/I-symporter (NIS) was expressed in Xenopus laevis oocytes and characterized using electrophysiological, tracer uptake, and electron microscopic methods. NIS activity was found to be electrogenic and Na+-dependent (Na+ >> Li+ >> H+). The apparent affinity constants for Na+ and I ... >> More

  The rat thyroid Na+/I-symporter (NIS) was expressed in Xenopus laevis oocytes and characterized using electrophysiological, tracer uptake, and electron microscopic methods. NIS activity was found to be electrogenic and Na+-dependent (Na+ >> Li+ >> H+). The apparent affinity constants for Na+ and I- were 28 +/- 3 mM and 33 +/-9 microM, respectively. Stoichiometry of Na+/anion cotransport was 2:1. NIS was capable of transporting a wide variety of anions (I-, ClO3-, SCN-, SeCN-, NO3-, Br-, BF4-, IO4-, BrO3-, but perchlorate (ClO4-) was not transported. In the absence of anion substrate, NIS exhibited a Na+-dependent leak current (approximately 35% of maximum substrate-induced current) with an apparent Na+ affinity of 74 +/-14 mM and a Hill coefficient (n) of 1. In response to step voltage changes, NIS exhibited current transients that relaxed with a time constant of 8-14 ms. Presteady-state charge movements (integral of the current transients) versus voltage relations obey a Boltzmann relation. The voltage for half-maximal charge translocation (V0.5) was -15 +/-3 mV, and the apparent valence of the movable charge was 1. Total charge was insensitive to [Na+]o, but V0.5 shifted to more negative potentials as [Na+]o was reduced. NIS charge movements are attributed to the conformational changes of the empty transporter within the membrane electric field. The turnover rate of NIS was >/=22 s-1 in the Na+ uniport mode and >/=36 s-1 in the Na+/I-cotransport mode. Transporter density in the plasma membrane was determined using freeze-fracture electron microscopy. Expression of NIS in oocytes led to a approximately 2. 5-fold increase in the density of plasma membrane protoplasmic face intramembrane particles. On the basis of the kinetic results, we propose an ordered simultaneous transport mechanism in which the binding of Na+ to NIS occurs first. << Less

  J. Biol. Chem. 272:27230-27238(1997) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.

• Surprising substrate versatility in SLC5A6: Na+-coupled I- transport by the human Na+/multivitamin transporter (hSMVT).

  de Carvalho F.D., Quick M.

  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 medic ... >> More

  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. << Less

  J. Biol. Chem. 286:131-137(2011) [PubMed] [EuropePMC]

• Mechanism of anion selectivity and stoichiometry of the Na+/I- symporter (NIS).

  Paroder-Belenitsky M., Maestas M.J., Dohan O., Nicola J.P., Reyna-Neyra A., Follenzi A., Dadachova E., Eskandari S., Amzel L.M., Carrasco N.

  I(-) uptake in the thyroid, the first step in thyroid hormone biosynthesis, is mediated by the Na(+)/I(-) symporter (NIS) with an electrogenic 2Na(+):1I(-) stoichiometry. We have obtained mechanistic information on NIS by characterizing the congenital I(-) transport defect-causing NIS mutant G93R. ... >> More

  I(-) uptake in the thyroid, the first step in thyroid hormone biosynthesis, is mediated by the Na(+)/I(-) symporter (NIS) with an electrogenic 2Na(+):1I(-) stoichiometry. We have obtained mechanistic information on NIS by characterizing the congenital I(-) transport defect-causing NIS mutant G93R. This mutant is targeted to the plasma membrane but is inactive. Substitutions at position 93 show that the longer the side chain of the neutral residue at this position, the higher the K(m) for the anion substrates. Unlike WT NIS, which mediates symport of Na(+) and the environmental pollutant perchlorate electroneutrally, G93T/N/Q/E/D NIS, strikingly, do it electrogenically with a 21 stoichiometry. Furthermore, G93E/Q NIS discriminate between anion substrates, a discovery with potential clinical relevance. A 3D homology model of NIS based on the structure of the bacterial Na(+)/galactose transporter identifies G93 as a critical player in the mechanism of the transporter: the changes from an outwardly to an inwardly open conformation during the transport cycle use G93 as a pivot. << Less

  Proc Natl Acad Sci U S A 108:17933-17938(2011) [PubMed] [EuropePMC]