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Costagliola
Anion selectivity by the sodium iodide symporter.Van Sande J, Massart C, Beauwens R, Schoutens A, Costagliola S, Dumont JE, Wolff J. Endocrinology. 2003 Jan;144(1):247-52.
"The iodide transporter of the thyroid (NIS) has been cloned by the group of Carrasco. The NIS-mediated transport was studied by electrophysiological methods in NIS-expressing Xenopus oocytes. Using this method, the anion selectivity of NIS was different from that previously reported for thyroid cells, whereas perchlorate and perrhenate were found not transported. In this study we compared the properties of human NIS, stably transfected in COS-7 cells to those of the transport in a thyroid cell line, the FRTL5 cells, by measuring the transport directly. We measured the uptake of (125)I(-), (186)ReO(4)(-), and (99m)TcO(4)(-) and studied the effect on it of known competing anions, i.e. ClO(4)(-), SCN(-), ClO(3)(-), ReO(4)(-), and Br(-). We conclude that the properties of the NIS transporter account by themselves for the properties of the thyroid iodide transporter as described previously in thyroid slices. The order of affinity was: ClO(4)(-) > ReO(4)(-) > I(-) >/= SCN(-) > ClO(3)(-) > Br(-). NIS is also inhibited by dysidenin (as in dog thyroid)."
Rarity of anti- Na+/I- symporter (NIS) antibody with iodide uptake inhibiting activity in autoimmune thyroid diseases (AITD).Chin HS, Chin DK, Morgenthaler NG, Vassart G, Costagliola S. J Clin Endocrinol Metab. 2000 Oct;85(10):3937-40.
"The search for antibody against the Na+/I- symporter (NIS) has seen conflicting results over the years. Prior to cloning of NIS, Raspe et al found iodide uptake inhibiting sera were rare in autoimmune thyroid diseases (AITD) while post-cloning, others reported the presence of antibody in 12-15% of Hashimoto's thyroiditis (HT) and 30-84% of Graves' disease (GD). To evaluate the role of NIS as a potential antigen in AITD, a stable COS 7 cell line expressing high level of functional hNIS was established which allowed the screening of large number of sera for iodide uptake inhibiting activity in a 96-well plate format. Five hundred and fourteen serum samples taken from normal subjects and patients with AITD, non-autoimmune thyroid diseases, and non-thyroid autoimmune diseases were assayed for presence of iodide uptake inhibiting activity. Under the influence of these sera, iodide uptake showed a normal frequency distribution and diminution of uptake 2 SDs below the mean of controls was observed with 14 sera. Among these, 7 that were available for further study were re-evaluated after dialysis and/or Ig G extraction. All 7 sera lost their iodide uptake inhibiting activity, indicating that the effects were not antibody mediated and unknown serum factors had been responsible. In conclusion, contrary to previous results, the present study indicates that antibodies capable of modulating NIS activity are rare in AITD."
Failure of membrane targeting causes the functional defect of two mutant sodium iodide symporters.Pohlenz J, Duprez L, Weiss RE, Vassart G, Refetoff S, Costagliola S. J Clin Endocrinol Metab. 2000 Jul;85(7):2366-9. [abstract only]
"Molecular cloning of the sodium/iodide symporter (NIS) allowed identification of NIS gene mutations in patients with iodide trapping defect. Whereas various mutant human (h) NIS molecules display loss of function when expressed by transfection in mammalian cells, the precise mechanism(s) responsible for the functional abnormality of these proteins remains unknown. With the aim to explore these mechanisms in three natural hNIS mutants identified previously in patients with iodide trapping defect (Q267E, S515X, and C272X), we have prepared tools allowing direct measurement of the protein at its normal location in the plasma membrane. A COS-7 cell line was made by transfection that stably expressed high levels of wild-type hNIS. It was used to screen by flow cytometry monoclonal antibodies (mAbs) prepared from mice immunized against hNIS. Genetic immunization was performed by im injection of a wild-type hNIS complementary DNA construct, because this procedure has demonstrated the ability to produce antibodies recognizing native membrane proteins. One mAb that recognized an epitope of hNIS exposed on the extracellular side of the plasma membrane was selected for further studies. The epitope was localized on the sixth putative extracellular loop of the protein on the basis that the mAb did not recognize rat NIS, which exhibits major sequence differences in this segment. When this mAb was used to test by flow cytometry the expression of the three mutant hNIS proteins in transfected COS-7 cells, it detected similar amounts of wild-type, Q267E, and the S515X hNIS molecules in permeabilized cells. In contrast, only the wild-type hNIS was detected at the surface of nonpermeabilized cells. The C272X hNIS truncation mutant was not detected in intact or permeabilized cells. This is consistent with the absence of the mAb epitope from this mutant, which is expected to lack the sixth extracellular loop. Our data demonstrate that faulty membrane targeting is implicated in the mechanisms causing iodide trapping defect in the Q267E and S515X natural hNIS mutants."
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