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

Tejram Sahu, Bertrand Boisson, Céline Lacroix, Emmanuel Bischoff, Quentin Richier, Pauline Formaglio, Sabine Thiberge, Irina Dobrescu, Robert Ménard, Patricia Baldacci

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1387-1397
Number of pages11
JournalEMBO Molecular Medicine
Volume6
Issue number11
DOIs
StatePublished - Nov 1 2014

Keywords

  • Iron
  • Liver stage
  • Plasmodium
  • Transporter
  • ZIP

ASJC Scopus subject areas

  • Molecular Medicine

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