The iodide transport defect-causing Y348D mutation in the Na+/I- symporter (NIS) renders the protein intrinsically inactive and impairs its targeting to the plasma membrane

Thyroid ◽  
2021 ◽  
Author(s):  
Andrea Reyna-Neyra ◽  
Lara Jung ◽  
Mayukh Chakrabarti ◽  
Mikel Suarez ◽  
L. Mario Amzel ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Iodide Transport ◽  
Transport Defect

scholarly journals Molecular Analysis of a Congenital Iodide Transport Defect: G543E Impairs Maturation and Trafficking of the Na+/I− Symporter

2005 ◽  
Vol 19 (11) ◽  
pp. 2847-2858 ◽  
Author(s):  
Antonio De la Vieja ◽  
Christopher S. Ginter ◽  
Nancy Carrasco
Keyword(s):  
Plasma Membrane ◽  
Amino Acid ◽  
Cell Surface ◽  
Molecular Analysis ◽  
Molecular Level ◽  
Membrane Glycoprotein ◽  
Amino Acid Substitutions ◽  
Mutant Proteins ◽  
Iodide Transport ◽  
Transport Defect

Abstract The Na+/I− symporter (NIS) is a key membrane glycoprotein that mediates active I− transport in the thyroid and other tissues. Upon isolation of the cDNA encoding NIS, 10 NIS mutations that cause congenital iodide transport defect have been identified. Three of these mutations (T354P, G395R, and Q267E) have been thoroughly characterized at the molecular level. All three NIS mutant proteins are correctly targeted to the plasma membrane; however, whereas Q267E displays minimal activity, T354P and G395R are inactive. Here, we show that in contrast to these mutants, G543E NIS matures only partially and is retained intracellularly; thus, it is not targeted properly to the cell surface, apparently because of faulty folding. These findings indicate that the G543 residue plays significant roles in NIS maturation and trafficking. Remarkably, NIS activity was rescued by small neutral amino acid substitutions (volume < 129 Å3) at this position, suggesting that G543 is in a tightly packed region of NIS.

scholarly journals Thyroid Gene Mutations in Pregnant and Breastfeeding Women Diagnosed With Transient Congenital Hypothyroidism: Implications for the Offspring’s Health

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria C. Opazo ◽  
Juan Carlos Rivera ◽  
Pablo A. Gonzalez ◽  
Susan M. Bueno ◽  
Alexis M. Kalergis ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Congenital Hypothyroidism ◽  
Gene Mutations ◽  
Genetic Variations ◽  
Hormone Deficiency ◽  
Iodide Transport ◽  
Transport Defect ◽  
Pregnancy And Lactation ◽  
Transient Congenital Hypothyroidism

Fetus and infants require appropriate thyroid hormone levels and iodine during pregnancy and lactation. Nature endorses the mother to supply thyroid hormones to the fetus and iodine to the lactating infant. Genetic variations on thyroid proteins that cause dyshormonogenic congenital hypothyroidism could in pregnant and breastfeeding women impair the delivery of thyroid hormones and iodine to the offspring. The review discusses maternal genetic variations in thyroid proteins that, in the context of pregnancy and/or breastfeeding, could trigger thyroid hormone deficiency or iodide transport defect that will affect the proper development of the offspring.

Plasma Membrane Carnitine Transport Defect

2009 ◽  
pp. 1655-1655
Author(s):  
Markus Braun-Falco ◽  
Henry J. Mankin ◽  
Sharon L. Wenger ◽  
Markus Braun-Falco ◽  
Stephan DiSean Kendall ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Transport Defect ◽  
Carnitine Transport

Inhibition of iodide accumulation by perchlorate and thiocyanate in a model of the thyroid iodide transport system

1983 ◽  
Vol 104 (4) ◽  
pp. 456-461 ◽  
Author(s):  
Koshi Saito ◽  
Kunihiro Yamamoto ◽  
Takaji Takai ◽  
Sho Yoshida
Keyword(s):  
Plasma Membrane ◽  
Transport System ◽  
Competitive Inhibitor ◽  
Biological Model ◽  
Phospholipid Vesicles ◽  
Iodide Transport ◽  
Plot Analysis ◽  
Soybean Phospholipids ◽  
Slight Depression ◽  
Burk Plot

Abstract. The manner of inhibition of thyroid I− accumulation by perchlorate (ClO4−) and thiocyanate (SCN−) was studied using a newly developed biological model of the I− transport system. ClO4− inhibited I− accumulation in phospholipid vesicles made from thyroid plasma membrane and soybean phospholipids by decreasing Na+-dependent I− influx. The anion did not at all induce I− leakage from the vesicles. On the basis of Lineweaver-Burk plot analysis, it did not change Vmax for I− concentration. These results suggest that ClO4− is a competitive inhibitor of thyroid I− transport. In contrast, SCN− did increase I− leakage from the phospholipid vesicles to diminish I− accumulation. This anion might cause only slight depression of Na+-dependent I− entry, if any. The results do not support the idea that SCN− may be a competitive inhibitor, in spite of the fact that the anion did not change Vmax for I− transport on the basis of Lineweaver-Burk plot analysis.

Sisters with Iodide Transport Defect Caused by a Mutation of the NIS Gene not Detected in Neonatal Mass Screening for Cretinism

1999 ◽  
Vol 8 (1) ◽  
pp. 35-41
Author(s):  
Hirotake Sawada ◽  
Shinobu Inoue ◽  
Tohru Sugimoto ◽  
Shigeki Nagamachi ◽  
Shinji Kosugi
Keyword(s):  
Mass Screening ◽  
Iodide Transport ◽  
Transport Defect ◽  
Nis Gene

The role of serum thyroglobulin concentration and thyroid ultrasound imaging in the detection of iodide transport defects in infants

1991 ◽  
Vol 124 (4) ◽  
pp. 405-410 ◽  
Author(s):  
Thomas Vulsma ◽  
Johan A. Rammeloo ◽  
Margareth H. Gons ◽  
Jan J. M. de Vijlder
Keyword(s):  
Ultrasound Imaging ◽  
Neonatal Screening ◽  
Ultrasound Image ◽  
High Serum ◽  
Thyroid Ultrasound ◽  
Serum Thyroglobulin ◽  
Iodide Transport ◽  
Thyroid Screening ◽  
Transport Defect ◽  
Neonatal Thyroid Screening

Abstract. When discovered by neonatal screening, a thyroid dyshormonogenesis is usually not recognized as a goitre. Especially a total iodide transport defect can easily be misclassified as thyroid agenesis, since radionuclide imaging cannot visualize the thyroid. We present the only iodide transport defect ever discovered in the Netherlands, the 35th reported in the literature, and the first one found exclusively as a result of neonatal screening. We demonstrate that iodide transport defects, in common with organification and deiodinase defects, can be distinguished from thyroid dysgenesis by demonstrating a normal or enlarged thyroid ultrasound image, and especially by measuring very high serum thyroglobulin levels (above 1000 pmol/l). In the presented case, an iodide-123 saliva-to-serum ratio near unity completed the etiologic classification. Measurement of serum thyroglobulin levels, in combination with thyroid ultrasound imaging, will improve the early identification of hereditary types of congenital hypothyroidism, and especially iodide transport defects, in patients found by neonatal thyroid screening.

scholarly journals TSH Regulates Pendrin Membrane Abundance and Enhances Iodide Efflux in Thyroid Cells

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 512-521 ◽  
Author(s):  
Liuska Pesce ◽  
Aigerim Bizhanova ◽  
Juan Carlos Caraballo ◽  
Whitney Westphal ◽  
Maria L. Butti ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Phosphorylation Site ◽  
Physiological Role ◽  
Thyroid Cells ◽  
Hormone Synthesis ◽  
Iodide Transport ◽  
Rat Thyroid ◽  
Kinase A

Thyroid hormones are essential for normal development and metabolism. Their synthesis requires transport of iodide into thyroid follicles. The mechanisms involving the apical efflux of iodide into the follicular lumen are poorly elucidated. The discovery of mutations in the SLC26A4 gene in patients with Pendred syndrome (congenital deafness, goiter, and defective iodide organification) suggested a possible role for the encoded protein, pendrin, as an apical iodide transporter. We determined whether TSH regulates pendrin abundance at the plasma membrane and whether this influences iodide efflux. Results of immunoblot and immunofluorescence experiments reveal that TSH and forskolin rapidly increase pendrin abundance at the plasma membrane through the protein kinase A pathway in PCCL-3 rat thyroid cells. The increase in pendrin membrane abundance correlates with a decrease in intracellular iodide as determined by measuring intracellular 125iodide and can be inhibited by specific blocking of pendrin. Elimination of the putative protein kinase A phosphorylation site T717A results in a diminished translocation to the membrane in response to forskolin. These results demonstrate that pendrin translocates to the membrane in response to TSH and suggest that it may have a physiological role in apical iodide transport and thyroid hormone synthesis.

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