Linked Life Data

14734652

Source:http://linkedlifedata.com/resource/pubmed/id/14734652

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 5
pubmed:dateCreated
2004-2-2
pubmed:abstractText
The Na(+)/I(-) symporter (NIS) is a key plasma membrane glycoprotein that mediates active iodide (I(-)) transport in the thyroid and other tissues. Since isolation of the cDNA encoding NIS (G. Dai, O. Levy, and N. Carrasco (1996) Nature 379, 458-460), ten mutations in NIS have been identified as causes of congenital iodide transport defect (ITD). Two of these mutations (T354P and G395R) have been thoroughly characterized at the molecular level. Both mutant NIS proteins are inactive but normally expressed and correctly targeted to the plasma membrane. The hydroxyl group at the beta-carbon of residue 354 is essential for NIS function, whereas the presence of a charged or large side-chain at position 395 interferes with NIS function. We report the extensive molecular analysis of the Q267E mutation in COS-7 cells transfected with rat or human Q267E NIS cDNA constructs. We used site-directed mutagenesis to engineer various residue substitutions into position 267. In contrast to previous suggestions that Q267E NIS was inactive, possibly because of a trafficking defect, we conclusively show that Q267E NIS is modestly active and properly targeted to the plasma membrane. Q267E NIS exhibited lower V(max) values for I(-) than wild-type NIS, suggesting that the decreased level of activity of Q267E NIS is due to a lower catalytic rate. That Q267E NIS retains even partial activity sets this ITD-causing mutant apart from T354P and G395R NIS. The presence of charged residues (of any polarity) other than Glu at position 267 rendered NIS inactive without affecting its expression or targeting, but substitution with neutral residues at this position was compatible with partial activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
677-87
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
The Q267E mutation in the sodium/iodide symporter (NIS) causes congenital iodide transport defect (ITD) by decreasing the NIS turnover number.
pubmed:affiliation
Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't