DMT1: Which metals does it transport?
| Autor: | Laura M. Garrick, Lin Zhao, Martin Knöpfel, Jerome A. Roth, Max Costa, Steven T. Singleton, Prasad N. Paradkar, H-C Kuo, Todd Davidson, Farida Vargas, Michael D. Garrick |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Gene isoform
Metal ion transport Endosome Nramp2 or SLC11A2 Voltage clamp Endogeny expression assay General Biochemistry Genetics and Molecular Biology Metal 03 medical and health sciences 0302 clinical medicine DCT1 Animals Humans competition between metal ions RNA Small Interfering Cation Transport Proteins lcsh:QH301-705.5 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology digestive oral and skin physiology Transporter Biological Transport General Medicine DMT1 Rats chemistry Biochemistry lcsh:Biology (General) Transferrin Metals visual_art Biophysics biology.protein visual_art.visual_art_medium Caco-2 Cells General Agricultural and Biological Sciences 030217 neurology & neurosurgery |
| Zdroj: | Biological Research, Vol 39, Iss 1, Pp 79-85 (2006) Biological Research, Volume: 39, Issue: 1, Pages: 79-85, Published: 2006 Biological Research v.39 n.1 2006 SciELO Chile CONICYT Chile instacron:CONICYT Scopus-Elsevier |
| ISSN: | 0717-6287 0716-9760 |
| Popis: | DMT1-Divalent Metal (Ion) Transporter 1 or SLC11A2/DCT1/Nramp2 - transports Fe2+ into the duodenum and out of the endosome during the transferrin cycle. DMTI also is important in non-transferrin bound iron uptake. It plays similar roles in Mn2+ trafficking. Voltage clamping showed that six other metals evoked currents, but it is unclear if these metals are substrates for DMT1. This report summarizes progress on which metals DMT1 transports, focusing on results from the authors' labs. We recently cloned 1A/+IRE and 2/-IRE DMT1 isoforms to generate HEK293 cell lines that express them in a tetracycline-inducible fashion, then compared induced expression to uninduced expression and to endogenous DMT1 expression. Induced expression increases approximately 50x over endogenous expression and approximately 10x over uninduced levels. Fe2+, Mn2+, Ni2+ and Cu1+ or Cu2+ are transported. We also explored competition between metal ions using this system because incorporation essentially represents DMT1 transport and find this order for transport affinity: Mn>?Cd>?Fe>Pb-Co-Ni>Zn. The effects of decreased DMT1 also could be examined. The Belgrade rat has diminished DMT1 function and thus provides ways of testing. A series of DNA constructs that generate siRNAs specific for DMT1 or certain DMT1 isoforms yield another way to test DMT1-based transport. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|