Dcytb (Cybrd1) functions as both a ferric and a cupric reductase in vitro.
MDCK cells expressing an inducible duodenal cytochrome b-green fluorescent protein (Dcytb-EGFP) fusion construct were used to investigate the function of Dcytb. The Dcytb-EGFP protein was targeted correctly to the plasma membrane, and cells displayed increased ferric and cupric reductase activities, which were greatly reduced in the presence of doxycycline. The data suggests that Dcytb plays a physiological role in both iron and copper uptake, through divalent metal transporter 1 (DMT1) and copper transporter 1, respectively. In support of this hypothesis, we show that 59Fe uptake was significantly enhanced in Dcytb-EGFP expressing MDCK cells which endogenously express DMT1.
Wyman
Steven
S
King's College London, Iron Metabolism Group, Nutritional Sciences Division, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, United Kingdom.
Simpson
Robert J
RJ
McKie
Andrew T
AT
Sharp
Paul A
PA
D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism; D002460:Cell Line; D003300:Copper / Q000378:metabolism*; D000079923:Copper Transporter 1; D003573:Cytochrome b Group / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D038181:FMN Reductase / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics; D017136:Ion Transport; D007501:Iron / Q000378:metabolism*; D051379:Mice; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D003300:Copper; D000079923:Copper Transporter 1; D003573:Cytochrome b Group; D038181:FMN Reductase; D049452:Green Fluorescent Proteins; D007501:Iron; D010088:Oxidoreductases; D011993:Recombinant Fusion Proteins; D000099236:Solute Carrier Family 11, Member 2; C490077:Slc31a1 protein, mouse; C485184:enhanced green fluorescent protein; C122172:cupric reductase (NADH-linked); C498909:Cybrd1 protein, mouse; C023903:ferric citrate iron reductase