title: The iron transporter ferroportin can also function as a manganese exporter.
abstract: The present study examined the hypothesis that the iron exporter ferroportin (FPN1/SLC40A1) can also mediate cellular export of the essential trace element manganese, using Xenopus laevis oocytes expressing human FPN1. When compared to oocytes expressing only the divalent metal transporter-1 (DMT1/NRAMP2), (54)Mn accumulation was lower in oocytes also expressing FPN1. FPN1-expressing oocytes exported more (54)Mn than control oocytes (26.6±0.6% versus 7.1±0.5%, respectively, over 4h at pH 7.4 when preloaded with approximately 16μM (54)Mn); however, there was no difference in (54)Mn uptake between control and FPN1-expressing oocytes. FPN1-mediated Mn export was concentration dependent and could be partially cis-inhibited by 100μM Fe, Co, and Ni, but not by Rb. In addition, Mn export ability was significantly reduced when the extracellular pH was reduced from 7.4 to 5.5, and when Na(+) was substituted with K(+) in the incubation media. These results indicate that Mn is a substrate for FPN1, and that this export process is inhibited by a low extracellular pH and by incubation in a high K(+) medium, indicating the involvement of transmembrane ion gradients in FPN1-mediated transport.
authors.affiliation: Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY, USA. Mike_Madejczyk@urmc.rochester.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Madejczyk
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Ballatori
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D056945:Hep G2 Cells; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D008345:Manganese / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D014982:Xenopus laevis; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D008345:Manganese; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2