Linked Life Data

15485485

Source:http://linkedlifedata.com/resource/pubmed/id/15485485

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-10-15
pubmed:abstractText
Three C-terminal variants of the human norepinephrine transporter (hNET) are known: the wild-type hNET in which exon 14 encodes the last seven amino acids and two variants with either three or 18 amino acids encoded by an alternatively spliced exon 15. In transfected HEK293 cells we compared by means of [(3)H]norepinephrine ([(3)H]NE) uptake and [(3)H]nisoxetine ([(3)H]NIS) binding the functional properties of the wild-type hNET with those of the more abundant long splice variant containing exon 15 (hNET-Ex15L) and of two artificial hNET mutants lacking either the last three (hNET-Ex14-4) or all seven (hNET-Ex14-0) C-terminal amino acids of exon 14. No differences among the NET isoforms were observed concerning the K(m) for uptake of NE and the K(D) for binding of NIS. However, compared with the wild-type hNET, the three isoforms (hNET-Ex15L, hNET-Ex14-4 and hNET-Ex14-0) showed a pronounced decrease in V(max) of [(3)H]NE uptake and B(max) of [(3)H]NIS binding which correlated with strongly reduced surface expression of the transporter isoforms. The decrease in surface expression of the hNET isoforms is probably a consequence of the lack of the three amino acids leucine, alanine and isoleucine at the C-terminal end which may represent a motif facilitating cell surface expression of the hNET. Expression of hNET-Ex15L exerted a dominant negative effect on plasma membrane expression of the wild-type hNET and thus may represent a novel mechanism for regulation of noradrenergic neurotransmission.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
91
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
537-46
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15485485-Alternative Splicing, pubmed-meshheading:15485485-Amino Acid Substitution, pubmed-meshheading:15485485-Binding, Competitive, pubmed-meshheading:15485485-Cells, Cultured, pubmed-meshheading:15485485-Exons, pubmed-meshheading:15485485-Fluoxetine, pubmed-meshheading:15485485-Humans, pubmed-meshheading:15485485-Kidney, pubmed-meshheading:15485485-Mutagenesis, Site-Directed, pubmed-meshheading:15485485-Norepinephrine, pubmed-meshheading:15485485-Norepinephrine Plasma Membrane Transport Proteins, pubmed-meshheading:15485485-Protein Isoforms, pubmed-meshheading:15485485-Protein Structure, Tertiary, pubmed-meshheading:15485485-Recombinant Fusion Proteins, pubmed-meshheading:15485485-Structure-Activity Relationship, pubmed-meshheading:15485485-Symporters, pubmed-meshheading:15485485-Transfection, pubmed-meshheading:15485485-Tritium
pubmed:year
2004
pubmed:articleTitle
Functional importance of the C-terminus of the human norepinephrine transporter.
pubmed:affiliation
Institute of Pharmacology and Toxicology, University of Bonn, D-53113 Bonn, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't