<scp>ZIPCO</scp>, a putative metal ion transporter, is crucial for <i>Plasmodium</i> liver‐stage development

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

doi:10.15252/emmm.201403868

Cited by 33 publications

(39 citation statements)

References 47 publications

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“…Regulation of iron is essential for cell survival and should also, therefore, be critical during the entire Plasmodium life cycle 23 24 25 26 . Iron withdrawal by the use of iron chelators has been explored as an antimalarial approach for decades 27 and novel compounds with improved pharmacokinetic properties are being investigated 23 24 .…”

Section: Discussionmentioning

confidence: 99%

A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium

et al. 2016

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Iron is an essential micronutrient but is also highly toxic. In yeast and plant cells, a key detoxifying mechanism involves iron sequestration into intracellular storage compartments, mediated by members of the vacuolar iron-transporter (VIT) family of proteins. Here we study the VIT homologue from the malaria parasites Plasmodium falciparum (PfVIT) and Plasmodium berghei (PbVIT). PfVIT-mediated iron transport in a yeast heterologous expression system is saturable (Km∼14.7 μM), and selective for Fe2+ over other divalent cations. PbVIT-deficient P. berghei lines (Pbvit−) show a reduction in parasite load in both liver and blood stages of infection in mice. Moreover, Pbvit− parasites have higher levels of labile iron in blood stages and are more sensitive to increased iron levels in liver stages, when compared with wild-type parasites. Our data are consistent with Plasmodium VITs playing a major role in iron detoxification and, thus, normal development of malaria parasites in their mammalian host.

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Section: Discussionmentioning

confidence: 99%

A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium

et al. 2016

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“…2A) (Annoura et al 2014) and ZIPCO, an iron transporter expressed on the late liver stage PPM (Fig. 2B) (Sahu et al 2014). Although an increasing number of PV and PVM proteins have been identified that play important roles in liver stage development, an important future goal is the comprehensive identification of all liver stage PVM, PV, and PPM proteins that will supersede the current identification of important players using candidate approaches.…”

Section: Liver Stage Developmentmentioning

confidence: 98%

Malaria Parasite Liver Infection and Exoerythrocytic Biology

Vaughan

Kappe

2017

Cold Spring Harb Perspect Med

114

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In their infection cycle, malaria parasites undergo replication and population expansions within the vertebrate host and the mosquito vector. Host infection initiates with sporozoite invasion of hepatocytes, followed by a dramatic parasite amplification event during liver stage parasite growth and replication within hepatocytes. Each liver stage forms up to 90,000 exoerythrocytic merozoites, which are in turn capable of initiating a blood stage infection. Liver stages not only exploit host hepatocyte resources for nutritional needs but also endeavor to prevent hepatocyte cell death and detection by the host's immune system. Research over the past decade has identified numerous parasite factors that play a critical role during liver infection and has started to delineate a complex web of parasite-host interactions that sustain successful parasite colonization of the mammalian host. Targeting the parasites' obligatory infection of the liver as a gateway to the blood, with drugs and vaccines, constitutes the most effective strategy for malaria eradication, as it would prevent clinical disease and onward transmission of the parasite.

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“…While not essential, it was found to be important to parasite development during the liver stage, and while transport function was not characterised directly, increasing extracellular iron could, in part, rescue P. berghei parasites in which ZIPCO was genetically disrupted [44]. The latter result, coupled with plasma membrane localisation, suggests that ZIPCO acts to import iron into the parasite [44]. The second is an orthologue of the vacuolar iron transporter, VIT, family, members of which are proposed to transport Fe 2+ into acidic vacuoles.…”

Section: Divalent Cation Transportmentioning

confidence: 99%

“…The first is an orthologue of the zinc/iron permease, ZIP, family (of which two exist in Plasmodium genomes), which is termed the ZIP domaincontaining protein, ZIPCO. While not essential, it was found to be important to parasite development during the liver stage, and while transport function was not characterised directly, increasing extracellular iron could, in part, rescue P. berghei parasites in which ZIPCO was genetically disrupted [44]. The latter result, coupled with plasma membrane localisation, suggests that ZIPCO acts to import iron into the parasite [44].…”

Section: Divalent Cation Transportmentioning

confidence: 99%

Transmembrane solute transport in the apicomplexan parasite Plasmodium

Staines

Moore

Slavic

et al. 2017

Emerging Topics in Life Sciences

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Apicomplexa are a large group of eukaryotic, single-celled parasites, with complex life cycles that occur within a wide range of different microenvironments. They include important human pathogens such as Plasmodium, the causal agent of malaria, and Toxoplasma, which causes toxoplasmosis most often in immunocompromised individuals. Despite environmental differences in their life cycles, these parasites retain the ability to obtain nutrients, remove waste products, and control ion balances. They achieve this flexibility by relying on proteins that can deliver and remove solutes. This reliance on transport proteins for essential functions makes these pathways excellent potential targets for drug development programmes. Transport proteins are frequently key mediators of drug resistance by their ability to remove drugs from their sites of action. The study of transport processes mediated by integral membrane proteins and, in particular, identification of their physiological functions and localisation, and differentiation from host orthologues has already established new validated drug targets. Our understanding of how apicomplexan parasites have adapted to changing environmental challenges has also increased through the study of their transporters. This brief introduction to membrane transporters of apicomplexans highlights recent discoveries focusing on Plasmodium and emphasises future directions.

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

Cited by 33 publications

References 47 publications

A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium

A vacuolar iron-transporter homologue acts as a detoxifier in Plasmodium

Malaria Parasite Liver Infection and Exoerythrocytic Biology

Transmembrane solute transport in the apicomplexan parasite Plasmodium

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