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 journalArticle

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
Externally publishedYes

Fingerprint

Plasmodium
Metals
Ions
Liver
Iron
Proteins
Parasites
Zinc
Plasmodium malariae
Plasmodium berghei
Ion Transport
Growth
Protein Domains
Culicidae
Malaria
Hepatocytes
Carrier Proteins
Pharmaceutical Preparations

Keywords

  • Iron
  • Liver stage
  • Plasmodium
  • Transporter
  • ZIP

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

Sahu, T., Boisson, B., Lacroix, C., Bischoff, E., Richier, Q., Formaglio, P., ... Baldacci, P. (2014). ZIPCO, a putative metal ion transporter, is crucial for Plasmodium liver-stage development. EMBO Molecular Medicine, 6(11), 1387-1397. https://doi.org/10.15252/emmm.201403868

ZIPCO, a putative metal ion transporter, is crucial for Plasmodium liver-stage development. / Sahu, Tejram; Boisson, Bertrand; Lacroix, Céline; Bischoff, Emmanuel; Richier, Quentin; Formaglio, Pauline; Thiberge, Sabine; Dobrescu, Irina; Ménard, Robert; Baldacci, Patricia.

In: EMBO Molecular Medicine, Vol. 6, No. 11, 01.11.2014, p. 1387-1397.

Research output: Contribution to journalArticle

Sahu, T, Boisson, B, Lacroix, C, Bischoff, E, Richier, Q, Formaglio, P, Thiberge, S, Dobrescu, I, Ménard, R & Baldacci, P 2014, 'ZIPCO, a putative metal ion transporter, is crucial for Plasmodium liver-stage development', EMBO Molecular Medicine, vol. 6, no. 11, pp. 1387-1397. https://doi.org/10.15252/emmm.201403868
Sahu, Tejram ; Boisson, Bertrand ; Lacroix, Céline ; Bischoff, Emmanuel ; Richier, Quentin ; Formaglio, Pauline ; Thiberge, Sabine ; Dobrescu, Irina ; Ménard, Robert ; Baldacci, Patricia. / ZIPCO, a putative metal ion transporter, is crucial for Plasmodium liver-stage development. In: EMBO Molecular Medicine. 2014 ; Vol. 6, No. 11. pp. 1387-1397.
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