Dictyostelium Nramp1, which is structurally and functionally similar to mammalian DMT1 transporter, mediates phagosomal iron efflux

The Nramp (Slc11) protein family is widespread in bacteria and eukaryotes, and mediates transport of divalent metals across cellular membranes. The social amoeba Dictyostelium discoideum has two Nramp proteins. Nramp1, like its mammalian ortholog (SLC11A1), is recruited to phagosomal and macropinoso...

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Main Authors:	Buracco, Simona, Peracino, Barbara, Cinquetti, Raffaella, Signoretto, Elena, Vollero, Alessandra, Imperiali, Francesca, Castagna, Michela, Bossi, Elena, Bozzaro, Salvatore
Format:	Online
Language:	English
Published:	The Company of Biologists 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582194/

id	pubmed-4582194
recordtype	oai_dc
spelling	pubmed-45821942015-10-06 Dictyostelium Nramp1, which is structurally and functionally similar to mammalian DMT1 transporter, mediates phagosomal iron efflux Buracco, Simona Peracino, Barbara Cinquetti, Raffaella Signoretto, Elena Vollero, Alessandra Imperiali, Francesca Castagna, Michela Bossi, Elena Bozzaro, Salvatore Research Article The Nramp (Slc11) protein family is widespread in bacteria and eukaryotes, and mediates transport of divalent metals across cellular membranes. The social amoeba Dictyostelium discoideum has two Nramp proteins. Nramp1, like its mammalian ortholog (SLC11A1), is recruited to phagosomal and macropinosomal membranes, and confers resistance to pathogenic bacteria. Nramp2 is located exclusively in the contractile vacuole membrane and controls, synergistically with Nramp1, iron homeostasis. It has long been debated whether mammalian Nramp1 mediates iron import or export from phagosomes. By selectively loading the iron-chelating fluorochrome calcein in macropinosomes, we show that Dictyostelium Nramp1 mediates iron efflux from macropinosomes in vivo. To gain insight in ion selectivity and the transport mechanism, the proteins were expressed in Xenopus oocytes. Using a novel assay with calcein, and electrophysiological and radiochemical assays, we show that Nramp1, similar to rat DMT1 (also known as SLC11A2), transports Fe2+ and manganese, not Fe3+ or copper. Metal ion transport is electrogenic and proton dependent. By contrast, Nramp2 transports only Fe2+ in a non-electrogenic and proton-independent way. These differences reflect evolutionary divergence of the prototypical Nramp2 protein sequence compared to the archetypical Nramp1 and DMT1 proteins. The Company of Biologists 2015-09-01 /pmc/articles/PMC4582194/ /pubmed/26208637 http://dx.doi.org/10.1242/jcs.173153 Text en © 2015. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Buracco, Simona Peracino, Barbara Cinquetti, Raffaella Signoretto, Elena Vollero, Alessandra Imperiali, Francesca Castagna, Michela Bossi, Elena Bozzaro, Salvatore
spellingShingle	Buracco, Simona Peracino, Barbara Cinquetti, Raffaella Signoretto, Elena Vollero, Alessandra Imperiali, Francesca Castagna, Michela Bossi, Elena Bozzaro, Salvatore Dictyostelium Nramp1, which is structurally and functionally similar to mammalian DMT1 transporter, mediates phagosomal iron efflux
author_facet	Buracco, Simona Peracino, Barbara Cinquetti, Raffaella Signoretto, Elena Vollero, Alessandra Imperiali, Francesca Castagna, Michela Bossi, Elena Bozzaro, Salvatore
author_sort	Buracco, Simona
title	Dictyostelium Nramp1, which is structurally and functionally similar to mammalian DMT1 transporter, mediates phagosomal iron efflux
title_short	Dictyostelium Nramp1, which is structurally and functionally similar to mammalian DMT1 transporter, mediates phagosomal iron efflux
title_full	Dictyostelium Nramp1, which is structurally and functionally similar to mammalian DMT1 transporter, mediates phagosomal iron efflux
title_fullStr	Dictyostelium Nramp1, which is structurally and functionally similar to mammalian DMT1 transporter, mediates phagosomal iron efflux
title_full_unstemmed	Dictyostelium Nramp1, which is structurally and functionally similar to mammalian DMT1 transporter, mediates phagosomal iron efflux
title_sort	dictyostelium nramp1, which is structurally and functionally similar to mammalian dmt1 transporter, mediates phagosomal iron efflux
description	The Nramp (Slc11) protein family is widespread in bacteria and eukaryotes, and mediates transport of divalent metals across cellular membranes. The social amoeba Dictyostelium discoideum has two Nramp proteins. Nramp1, like its mammalian ortholog (SLC11A1), is recruited to phagosomal and macropinosomal membranes, and confers resistance to pathogenic bacteria. Nramp2 is located exclusively in the contractile vacuole membrane and controls, synergistically with Nramp1, iron homeostasis. It has long been debated whether mammalian Nramp1 mediates iron import or export from phagosomes. By selectively loading the iron-chelating fluorochrome calcein in macropinosomes, we show that Dictyostelium Nramp1 mediates iron efflux from macropinosomes in vivo. To gain insight in ion selectivity and the transport mechanism, the proteins were expressed in Xenopus oocytes. Using a novel assay with calcein, and electrophysiological and radiochemical assays, we show that Nramp1, similar to rat DMT1 (also known as SLC11A2), transports Fe2+ and manganese, not Fe3+ or copper. Metal ion transport is electrogenic and proton dependent. By contrast, Nramp2 transports only Fe2+ in a non-electrogenic and proton-independent way. These differences reflect evolutionary divergence of the prototypical Nramp2 protein sequence compared to the archetypical Nramp1 and DMT1 proteins.
publisher	The Company of Biologists
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582194/
_version_	1613479511717838848

Dictyostelium Nramp1, which is structurally and functionally similar to mammalian DMT1 transporter, mediates phagosomal iron efflux

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