Related Experiment Video
Updated: May 11, 2026
Understanding the Development of Compensatory Pathways in a Mutant Malaria Parasite Harbouring Hypomorphic Allele of Plant-Like Kinases
Published on: November 22, 2024
The exported protein PbCP1 localises to cleft-like structures in the rodent malaria parasite Plasmodium berghei
Silvia Haase1, Eric Hanssen, Kathryn Matthews
1School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
Abstract:
Protein export into the host red blood cell is one of the key processes in the pathobiology of the malaria parasite Plasmodiumtrl falciparum, which extensively remodels the red blood cell to ensure its virulence and survival. In this study, we aimed to shed further light on the protein export mechanisms in the rodent malaria parasite P. berghei and provide further proof of the conserved nature of host cell remodeling in Plasmodium spp. Based on the presence of an export motif (R/KxLxE/Q/D) termed PEXEL (Plasmodium export element), we have generated transgenic P. berghei parasite lines expressing GFP chimera of putatively exported proteins and analysed one of the newly identified exported proteins in detail. This essential protein, termed PbCP1 (P. berghei Cleft-like Protein 1), harbours an atypical PEXEL motif (RxLxY) and is further characterised by two predicted transmembrane domains (2TMD) in the C-terminal end of the protein. We have functionally validated the unusual PEXEL motif in PbCP1 and analysed the role of the 2TMD region, which is required to recruit PbCP1 to discrete membranous structures in the red blood cell cytosol that have a convoluted, vesico-tubular morphology by electron microscopy. Importantly, this study reveals that rodent malaria species also induce modifications to their host red blood cell.
Insights
Malaria parasites remodel red blood cells using protein export. This study identifies a new exported protein, PbCP1, in P. berghei, revealing conserved host cell modification mechanisms in Plasmodium species.
Area of Science:
- Malariology
- Molecular Parasitology
- Cell Biology
Background:
- Protein export into host red blood cells is crucial for malaria parasite virulence.
- Plasmodium falciparum extensively remodels host cells, but export mechanisms in other species are less understood.
Purpose of the Study:
- Investigate protein export mechanisms in the rodent malaria parasite P. berghei.
- Provide evidence for conserved host cell remodeling in Plasmodium species.
- Characterize a newly identified exported protein, PbCP1.
Main Methods:
- Generated transgenic P. berghei parasite lines expressing GFP chimeras of putatively exported proteins.
- Utilized the Plasmodium export element (PEXEL) motif for protein identification.
- Analyzed PbCP1, including its atypical PEXEL motif and two transmembrane domains (2TMD).
- Employed electron microscopy to visualize protein localization.
Main Results:
- Identified and characterized PbCP1, an essential protein with an atypical PEXEL motif (RxLxY) and 2TMD.
- Functionally validated the PEXEL motif in PbCP1.
- Demonstrated that the 2TMD region recruits PbCP1 to specific membranous structures within the red blood cell cytosol.
- Observed convoluted, vesico-tubular morphology of these structures via electron microscopy.
- Confirmed that rodent malaria species induce host red blood cell modifications.
Conclusions:
- The PEXEL motif and protein export machinery are conserved across Plasmodium species.
- PbCP1 plays a role in host cell modification, mediated by its unique structural features.
- Rodent malaria parasites, like P. berghei, actively remodel their host red blood cells, highlighting conserved pathobiology.
