Abstract

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 four out of the six membrane transporters are essential 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 and functionally conserved within the genus Plasmodium. Overall, we reveal the importance of four orphan transporters to blood stage P. falciparum development, which have diverse intracellular localizations and putative functions.

Competing Interest Statement

The authors have declared no competing interest.

Details

Title
PMRT1, a Plasmodium specific parasite plasma membrane transporter is essential for asexual and sexual blood stage development
Author
Jan Stephan Wichers; Mesén-Ramírez, Paolo; Yu-Strzelczyk, Jing; Fuchs, Gwendolin; Stäcker, Jan; Heidrun Von Thien; Alder, Arne; Henshall, Isabelle; Liffner, Benjamin; Nagel, Georg; Löw, Christian; Wilson, Danny W; Spielmann, Tobias; Gao, Shiqiang; Gilberger, Tim; Bachmann, Anna; Strauss, Jan
University/institution
Cold Spring Harbor Laboratory Press
Section
New Results
Publication year
2022
Publication date
Mar 12, 2022
Publisher
Cold Spring Harbor Laboratory Press
ISSN
2692-8205
Source type
Working Paper
Language of publication
English
ProQuest document ID
2613416472
Copyright
© 2022. This article is published under http://creativecommons.org/licenses/by/4.0/ (“the License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.