Characterization of Apicomplexan Amino Acid Transporters (ApiATs) in the Malaria Parasite Plasmodium falciparum

Wichers, Jan Stephan; Gelder, Carolina van; Fuchs, Gwendolin; Ruge, Julia M.; Pietsch, Emma; Ferreira, Josie L.; Safavi, Soraya; Thien, Heidrun von; Burda, Paul‐Christian; Mesén-Ramírez, Paolo; Spielmann, Tobias; Strauss, Jan; Gilberger, Tim‐Wolf; Bachmann, Anna

doi:10.1128/msphere.00743-21

Cited by 10 publications

(11 citation statements)

References 82 publications

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“…(A) Live cell microscopy of 3D7-iGP- Pf PMRT1-GFP parasites across the complete gametocyte development. White arrowheads indicate remaining GDV1-GFP signal observed in close proximity to the Hoechst signal, as previously reported ( 59 , 94 , 102 , 103 ). (B) Live cell microscopy of Pf PMRT1-GFP parasites expressing the PPM marker Lyn-mCherry.…”

Section: Resultssupporting

confidence: 67%

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PMRT1, a Plasmodium -Specific Parasite Plasma Membrane Transporter, Is Essential for Asexual and Sexual Blood Stage Development

Wichers

Mesén-Ramírez

Fuchs

et al. 2022

mBio

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Section: Resultssupporting

confidence: 67%

“…glmS-based knockdown experiments in gametocytes were performed as described previously ( 94 ). Briefly, synchronized ring stage cultures were induced by the addition of shield-1.…”

Section: Methodsmentioning

confidence: 99%

PMRT1, a Plasmodium -Specific Parasite Plasma Membrane Transporter, Is Essential for Asexual and Sexual Blood Stage Development

Wichers

Mesén-Ramírez

Fuchs

et al. 2022

mBio

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“… (A) Live cell microscopy of 3D7-iGP- Pf PMRT1-GFP parasites across the complete gametocyte development. White arrow heads indicate remaining GDV1-GFP signal observed in close proximity to the Hoechst signal, as previously reported (59, 94, 102, 103). (B) Live cell microscopy of Pf PMRT1-GFP parasites expressing the PPM marker Lyn-mCherry.…”

Section: Resultssupporting

confidence: 65%

PMRT1, aPlasmodiumspecific parasite plasma membrane transporter is essential for asexual and sexual blood stage development

Wichers

Mesén-Ramírez

Yu-Strzelczyk

et al. 2021

Preprint

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Membrane transport proteins perform crucial roles in cell physiology. The obligate intracellular parasite Plasmodium falciparum, an agent of human malaria, relies on membrane transport proteins for the uptake of nutrients from the host, disposal of metabolic waste, exchange of metabolites between organelles and generation and maintenance of transmembrane electrochemical gradients for its growth and replication within human erythrocytes. Despite their importance for Plasmodium cellular physiology, the functional roles of a number of membrane transport proteins remain unclear, which is particularly true for orphan membrane transporters that have no or limited sequence homology to transporter proteins in other evolutionary lineages. Therefore, in the current study, we applied endogenous tagging, targeted gene disruption, conditional knockdown and knockout approaches to investigate the subcellular localization and essentiality of six membrane transporters during intraerythrocytic development of P. falciparum parasites. They are localized at different subcellular structures – the food vacuole, the apicoplast, and the parasite plasma membrane – and showed essentiality of four out of the six membrane transporters during asexual development. Additionally, the plasma membrane resident transporter 1 (PMRT1, PF3D7_1135300), a unique Plasmodium-specific plasma membrane transporter, was shown to be essential for gametocytogenesis. Heterologous expression of wild-type and mutation constructs in Xenopus laevis oocytes indicated ion transport upon membrane hyperpolarization and a functional role of negatively charged amino acids protruding into the parasitophorous vacuole lumen. Overall, we reveal the importance of four orphan transporters to blood stage P. falciparum development and provide the first functional characterization of PfPMRT1, an essential parasite membrane transporter.

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“…The other three genes investigated in the same study were PfApiAT2, PfApiAT4, and PfApiAT10. All four PfApiATs were localized on the plasma membrane of asexual blood stage parasites and gametocytes [70]. Individual inactivation of each of these genes found only a minor reduction in parasite growth for PfApiAT2 and PfApiAT4, while the absence of PfApiAT8 and PfApiAT10 caused no apparent phenotype.…”

Section: Amino Acid Transportersmentioning

confidence: 99%

“…Ablation of PbApiAT8 resulted in significantly impaired microgamete formation and parasite motility in the sexual cycle [72]. In a very recent study [70], localization and essentiality of four ApiAT family members of P. falciparum during intraerythrocytic development has been investigated, including the homologue of PbApiAT8, PfApiAT8. Surprisingly, deletion of PfApiAT8 had no impact on gametocyte development and morphology.…”

Section: Amino Acid Transportersmentioning

confidence: 99%

An Uninvited Seat at the Dinner Table: How Apicomplexan Parasites Scavenge Nutrients from the Host

et al. 2021

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Obligate intracellular parasites have evolved a remarkable assortment of strategies to scavenge nutrients from the host cells they parasitize. Most apicomplexans form a parasitophorous vacuole (PV) within the invaded cell, a replicative niche within which they survive and multiply. As well as providing a physical barrier against host cell defense mechanisms, the PV membrane (PVM) is also an important site of nutrient uptake that is essential for the parasites to sustain their metabolism. This means nutrients in the extracellular milieu are separated from parasite metabolic machinery by three different membranes, the host plasma membrane, the PVM, and the parasite plasma membrane (PPM). In order to facilitate nutrient transport from the extracellular environment into the parasite itself, transporters on the host cell membrane of invaded cells can be modified by secreted and exported parasite proteins to maximize uptake of key substrates to meet their metabolic demand. To overcome the second barrier, the PVM, apicomplexan parasites secrete proteins contained in the dense granules that remodel the vacuole and make the membrane permissive to important nutrients. This bulk flow of host nutrients is followed by a more selective uptake of substrates at the PPM that is operated by specific transporters of this third barrier. In this review, we recapitulate and compare the strategies developed by Apicomplexa to scavenge nutrients from their hosts, with particular emphasis on transporters at the parasite plasma membrane and vacuolar solute transporters on the parasite intracellular digestive organelle.

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Characterization of Apicomplexan Amino Acid Transporters (ApiATs) in the Malaria Parasite Plasmodium falciparum

Abstract: Malaria parasites live and multiply inside cells. To facilitate their extremely fast intracellular proliferation, they hijack and transform their host cells.

Cited by 10 publications

References 82 publications

PMRT1, a Plasmodium -Specific Parasite Plasma Membrane Transporter, Is Essential for Asexual and Sexual Blood Stage Development

PMRT1, a Plasmodium -Specific Parasite Plasma Membrane Transporter, Is Essential for Asexual and Sexual Blood Stage Development

PMRT1, aPlasmodiumspecific parasite plasma membrane transporter is essential for asexual and sexual blood stage development

An Uninvited Seat at the Dinner Table: How Apicomplexan Parasites Scavenge Nutrients from the Host

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