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 language | English (US) |
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Pages (from-to) | 1387-1397 |
Number of pages | 11 |
Journal | EMBO Molecular Medicine |
Volume | 6 |
Issue number | 11 |
DOIs | |
State | Published - Nov 1 2014 |
Externally published | Yes |
Keywords
- Iron
- Liver stage
- Plasmodium
- Transporter
- ZIP
ASJC Scopus subject areas
- Molecular Medicine