| The human concentrative nucleoside transporter-3 C602R variant shows impaired sorting to lipid rafts and altered specificity for nucleoside-derived drugs. | |
| | |
MedLine Citation:
|
PMID: 20421346 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The human concentrative nucleoside transporter-3 C602R (hCNT3C602R), a recently identified human concentrative nucleoside transporter-3 (hCNT3) variant, has been shown to interact with natural nucleosides with apparent K(m) values similar to those of the wild-type transporter, although binding of one of the two sodium ions required for nucleoside translocation is impaired, resulting in decreased V(max) values (Mol Pharmacol 73:379-386, 2008). We have further analyzed the properties of this hCNT3 variant by determining its localization in plasma membrane lipid domains and its interaction with nucleoside-derived drugs used in anticancer and antiviral therapies. When expressed heterologously in HeLa cells, wild-type hCNT3 localized to both lipid raft and nonlipid raft domains. Treatment of cells with the cholesterol-depleting agent methyl-beta-cyclodextrin resulted in a marked decrease in hCNT3-related transport activity that was associated with the loss of wild-type hCNT3 from lipid rafts. It is noteworthy that although exogenously expressed hCNT3C602R was present in nonlipid raft domains at a level similar to that of the wild-type transporter, the mutant transporter was present at much lower amounts in lipid rafts. A substrate profile analysis showed that interactions with a variety of nucleoside-derived drugs were altered in the hCNT3C602R variant and revealed that sugar hydroxyl residues are key structural determinants for substrate recognition by the hCNT3C602R variant. |
| | |
Authors:
|
Ekaitz Errasti-Murugarren; Miriam Molina-Arcas; F Javier Casado; Marçal Pastor-Anglada |
Related Documents
:
|
19854186 - Formation and regulation of lipid microdomains in cell membranes: theory, modeling, and... 16024806 - Individual palmitoyl residues serve distinct roles in h-ras trafficking, microlocalizat... 17993486 - Raft composition at physiological temperature and ph in the absence of detergents. 11676926 - Phosphatidylinositol 3-phosphate is generated in phagosomal membranes. 11955146 - Charge localization in collision-induced multiple ionization of van der waals clusters ... 20009266 - Tree ring imprints of long-term changes in climate in western himalaya, india. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-26 |
Journal Detail:
|
Title: Molecular pharmacology Volume: 78 ISSN: 1521-0111 ISO Abbreviation: Mol. Pharmacol. Publication Date: 2010 Aug |
Date Detail:
|
Created Date: 2010-07-15 Completed Date: 2010-08-03 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0035623 Medline TA: Mol Pharmacol Country: United States |
Other Details:
|
Languages: eng Pagination: 157-65 Citation Subset: IM |
Affiliation:
|
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona and CIBER EHD, Avda Diagonal 645, Edifici annex, Planta-1, 08028 Barcelona, Spain. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Base Sequence Cells, Cultured DNA Primers Dogs Hela Cells Humans Lipid Metabolism* Membrane Transport Proteins / genetics, metabolism* Mutagenesis, Site-Directed Nucleosides / pharmacology* Polymorphism, Genetic |
| Chemical | |
Reg. No./Substance:
|
0/DNA Primers; 0/Membrane Transport Proteins; 0/Nucleosides; 0/cif nucleoside transporter |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Patients with RA in remission on TNF blockers: when and in whom can TNF blocker therapy be stopped?
Next Document: Inhibition of human T-cell proliferation by mammalian target of rapamycin (mTOR) antagonists require...