Na+/i- symporter activity requires a small and uncharged amino acid residue at position 395

O. Dohán, M. Verónica Gavrielides, Christopher Ginter, L. Mario Amzel, Nancy Carrasco

Research output: Contribution to journalArticle

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Abstract

Active iodide uptake in the thyroid is mediated by the Na+/I- symporter (NIS), a key plasma membrane glycoprotein. Several NIS mutations have been shown to cause I- transport defect, a condition that, if untreated, can lead to congenital hypothyroidism and, ultimately, cretinism. The study of I- transport defect-causing NIS mutations provides valuable insights into the structure-function and mechanistic properties of NIS. Here we report the thorough analysis of the G395R NIS mutation. We observed no I- uptake activity at saturating or even supersaturating external I- concentrations in COS-7 cells transiently transfected with G395R NIS cDNA, even though we demonstrated normal expression of G395R NIS and proper targeting to the plasma membrane. Several amino acid substitutions at position 395 showed that the presence of an uncharged amino acid residue with a small side chain at position 395 is required for NIS function, suggesting that glycine 395 is located in a tightly packed region of NIS. Substitutions of large amino acid residues at position 395 resulted in lower Vmax without affecting Km values for I- and Na+, suggesting that these residues hamper the Na+/I- coupling reaction.

Original languageEnglish
Pages (from-to)1893-1902
Number of pages10
JournalMolecular Endocrinology
Volume16
Issue number8
DOIs
Publication statusPublished - 2002

Fingerprint

Symporters
Amino Acids
Congenital Hypothyroidism
Amino Acid Substitution
Mutation
Cell Membrane
COS Cells
Membrane Glycoproteins
Iodides
Glycine
Thyroid Gland
Complementary DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Na+/i- symporter activity requires a small and uncharged amino acid residue at position 395. / Dohán, O.; Verónica Gavrielides, M.; Ginter, Christopher; Mario Amzel, L.; Carrasco, Nancy.

In: Molecular Endocrinology, Vol. 16, No. 8, 2002, p. 1893-1902.

Research output: Contribution to journalArticle

Dohán, O, Verónica Gavrielides, M, Ginter, C, Mario Amzel, L & Carrasco, N 2002, 'Na+/i- symporter activity requires a small and uncharged amino acid residue at position 395', Molecular Endocrinology, vol. 16, no. 8, pp. 1893-1902. https://doi.org/10.1210/me.2002-0071
Dohán, O. ; Verónica Gavrielides, M. ; Ginter, Christopher ; Mario Amzel, L. ; Carrasco, Nancy. / Na+/i- symporter activity requires a small and uncharged amino acid residue at position 395. In: Molecular Endocrinology. 2002 ; Vol. 16, No. 8. pp. 1893-1902.
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AU - Carrasco, Nancy

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