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

EMBO Molecular Medicine

Tejram Sahu²  Bertrand Boisson²  Céline Lacroix²  Emmanuel Bischoff¹  Quentin Richier²  Pauline Formaglio²  Sabine Thiberge²  Irina Dobrescu²  Robert Ménard² 

[1] Institut Pasteur, Plateforme Puces à ADN Génopole, Paris Cedex 15, France;Institut Pasteur, Unité de Biologie et Génétique du Paludisme, Paris Cedex 15, France

关键词: iron;    liver stage;    Plasmodium;    transporter;    ZIP;   

DOI  :  10.15252/emmm.201403868

来源: Wiley

【 摘 要 】

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.

Synopsis

ZIPCO is a novel Plasmodium berghei ZIP family protein, which might be involved in the transport of iron and possibly zinc. Parasites lacking ZIPCO present a normal blood phase but display a major developmental block in the host liver, which can be rescued by iron and zinc supplementation.

• ZIPCO is a newly identified Plasmodium protein belonging to the ZRT, IRT-like Protein (ZIP) family.
• Plasmodium berghei parasites lacking ZIPCO have no defect during the blood phase of malaria but display a major developmental block in the host liver.
• The growth defect is rescued by iron and zinc supplementation.
• This is first time that a ZIP protein has been shown to be important for the Plasmodium life cycle.

【 授权许可】

CC BY   
© 2014 Institut Pasteur. Published under the terms of the CC BY 4.0 license

Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.