title: ZIPCO, a putative metal ion transporter, is crucial for Plasmodium liver-stage development.
abstract: The malaria parasite, Plasmodium, requires iron for growth, but how it imports iron remains unknown. We characterize here a protein that belongs to the ZIP (Zrt-, Irt-like Protein) family of metal ion transport proteins and have named ZIP domain-containing protein (ZIPCO). Inactivation of the ZIPCO-encoding gene in Plasmodium berghei, while not affecting the parasite's ability to multiply in mouse blood and to infect mosquitoes, greatly impairs its capacity to develop inside hepatocytes. Iron/zinc supplementation and depletion experiments suggest that ZIPCO is required for parasite utilization of iron and possibly zinc, consistent with its predicted function as a metal transporter. This is the first report of a ZIP protein having a crucial role in Plasmodium liver-stage development, as well as the first metal ion transporter identified in Plasmodium pre-erythrocytic stages. Because of the drastic dependence on iron of Plasmodium growth, ZIPCO and related proteins might constitute attractive drug targets to fight against malaria.
authors.affiliation: Institut Pasteur Unité de Biologie et Génétique du Paludisme, Paris Cedex 15, France Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, Rockville, MD, USA.
authors.forename: Tejram
authors.initials: T
authors.lastname: Sahu
authors.affiliation: Institut Pasteur Unité de Biologie et Génétique du Paludisme, Paris Cedex 15, France St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, USA.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Boisson
authors.affiliation: Institut Pasteur Unité de Biologie et Génétique du Paludisme, Paris Cedex 15, France Institut de Biologie et Chimie des Protéines, Lyon Cedex 07, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Lacroix
authors.affiliation: Institut Pasteur Plateforme Puces à ADN Génopole, Paris Cedex 15, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bischoff
authors.affiliation: Institut Pasteur Unité de Biologie et Génétique du Paludisme, Paris Cedex 15, France.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Richier
authors.affiliation: Institut Pasteur Unité de Biologie et Génétique du Paludisme, Paris Cedex 15, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Formaglio
authors.affiliation: Institut Pasteur Unité de Biologie et Génétique du Paludisme, Paris Cedex 15, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Thiberge
authors.affiliation: Institut Pasteur Unité de Biologie et Génétique du Paludisme, Paris Cedex 15, France.
authors.forename: Irina
authors.initials: I
authors.lastname: Dobrescu
authors.affiliation: Institut Pasteur Unité de Biologie et Génétique du Paludisme, Paris Cedex 15, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Ménard
authors.affiliation: Institut Pasteur Unité de Biologie et Génétique du Paludisme, Paris Cedex 15, France patricia.baldacci@pasteur.fr.
authors.forename: Patricia
authors.initials: P
authors.lastname: Baldacci
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles; D005260:Female; D055786:Gene Knockout Techniques; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000469:parasitology; D006801:Humans; D007477:Ions / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000469:parasitology*; D008288:Malaria / Q000469:parasitology*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010802:Phylogeny; D010962:Plasmodium berghei / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015032:Zinc / Q000378:metabolism
chemical_list: D007477:Ions; D026901:Membrane Transport Proteins; D007501:Iron; D015032:Zinc
keywords: Plasmodium; ZIP; iron; liver stage; transporter