title: DMT1: which metals does it transport?
abstract: 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.
authors.affiliation: Department of Biochemistry, SUNY at Buffalo, Buffalo, NY 14214, USA. mgarrick@buffalo.edu
authors.forename: Michael D
authors.initials: MD
authors.lastname: Garrick
authors.forename: Steven T
authors.initials: ST
authors.lastname: Singleton
authors.forename: Farida
authors.initials: F
authors.lastname: Vargas
authors.forename: H-C
authors.initials: HC
authors.lastname: Kuo
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Martin
authors.initials: M
authors.lastname: Knöpfel
authors.forename: Todd
authors.initials: T
authors.lastname: Davidson
authors.forename: Max
authors.initials: M
authors.lastname: Costa
authors.forename: Prasad
authors.initials: P
authors.lastname: Paradkar
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Roth
authors.forename: Laura M
authors.initials: LM
authors.lastname: Garrick
mesh_terms: D000818:Animals; D001692:Biological Transport; D018938:Caco-2 Cells; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008670:Metals / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D008670:Metals; D034741:RNA, Small Interfering; D000099236:Solute Carrier Family 11, Member 2