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EMBO Mol Med. 2014 Nov;6(11):1387-97. doi: 10.15252/emmm.201403868.

ZIPCO, a putative metal ion transporter, is crucial for Plasmodium liver-stage development.

Author information

1
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.
2
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.
3
Institut Pasteur Unité de Biologie et Génétique du Paludisme, Paris Cedex 15, France Institut de Biologie et Chimie des Protéines, Lyon Cedex 07, France.
4
Institut Pasteur Plateforme Puces à ADN Génopole, Paris Cedex 15, France.
5
Institut Pasteur Unité de Biologie et Génétique du Paludisme, Paris Cedex 15, France.
6
Institut Pasteur Unité de Biologie et Génétique du Paludisme, Paris Cedex 15, France patricia.baldacci@pasteur.fr.

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.

KEYWORDS:

Plasmodium; ZIP; iron; liver stage; transporter

PMID:
25257508
PMCID:
PMC4237467
DOI:
10.15252/emmm.201403868
[Indexed for MEDLINE]
Free PMC Article

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