RGD Reference Report - Molecular characterization of V59E NIS, a Na+/I- symporter mutant that causes congenital I- transport defect. - Rat Genome Database

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Molecular characterization of V59E NIS, a Na+/I- symporter mutant that causes congenital I- transport defect.

Authors: Reed-Tsur, Mia D  De la Vieja, Antonio  Ginter, Christopher S  Carrasco, Nancy 
Citation: Reed-Tsur MD, etal., Endocrinology. 2008 Jun;149(6):3077-84. doi: 10.1210/en.2008-0027. Epub 2008 Mar 13.
RGD ID: 15090852
Pubmed: PMID:18339708   (View Abstract at PubMed)
PMCID: PMC2408800   (View Article at PubMed Central)
DOI: DOI:10.1210/en.2008-0027   (Journal Full-text)

I(-) is actively transported into thyrocytes via the Na+/I(-) symporter (NIS), a key glycoprotein located on the basolateral plasma membrane. The cDNA encoding rat NIS was identified in our laboratory, where an extensive structure/function characterization of NIS is being conducted. Several NIS mutants have been identified as causes of congenital I(-) transport defect (ITD), including V59E NIS. ITD is characterized by low thyroid I(-) uptake, low saliva/plasma I(-) ratio, hypothyroidism, and goiter and may cause mental retardation if untreated. Studies of other ITD-causing NIS mutants have revealed valuable information regarding NIS structure/function. V59E NIS was reported to exhibit as much as 30% of the activity of wild-type NIS. However, this observation was at variance with the patients' phenotype of total lack of activity. We have thoroughly characterized V59E NIS and studied several amino acid substitutions at position 59. We demonstrated that, in contrast to the previous report, V59E NIS is inactive, although it is properly targeted to the plasma membrane. Glu and all other charged amino acids or Pro at position 59 also yielded nonfunctional NIS proteins. However, I(-) uptake was rescued to different degrees by the other substitutions. Although the Km values for Na+ and I(-) were not altered in these active mutants, we found that the structural requirement for NIS function at position 59 is a neutral, helix-promoting amino acid. This result suggests that the region that contains V59 may be involved in intramembrane helix-helix interactions during the transport cycle without being in direct contact with the substrates.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
iodide transmembrane transport involved_inIMP 15090852PMID:18339708ARUK-UCL 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
plasma membrane is_active_inIDA 15090852PMID:18339708ARUK-UCL 
plasma membrane located_inIDA 15090852PMID:18339708ARUK-UCL 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
iodide transmembrane transporter activity enablesIMP 15090852PMID:18339708ARUK-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Slc5a5  (solute carrier family 5 member 5)


Additional Information