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Updated: Jul 29, 2026

Selection of Plasmodium falciparum Parasites for Cytoadhesion to Human Brain Endothelial Cells
Published on: January 3, 2012
Trafficking and assembly of the cytoadherence complex in Plasmodium falciparum-infected human erythrocytes
M E Wickham1, M Rug, S A Ralph
1The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Melbourne 3050, Australia.
Abstract:
After invading human erythrocytes, the malarial parasite Plasmodium falciparum, initiates a remarkable process of secreting proteins into the surrounding erythrocyte cytoplasm and plasma membrane. One of these exported proteins, the knob-associated histidine-rich protein (KAHRP), is essential for microvascular sequestration, a strategy whereby infected red cells adhere via knob structures to capillary walls and thus avoid being eliminated by the spleen. This cytoadherence is an important factor in many of the deaths caused by malaria. Green fluorescent protein fusions and fluorescence recovery after photobleaching were used to follow the pathway of KAHRP deployment from the parasite endomembrane system into an intermediate depot between parasite and host, then onwards to the erythrocyte cytoplasm and eventually into knobs. Sequence elements essential to individual steps in the pathway are defined and we show that parasite-derived structures, known as Maurer's clefts, are an elaboration of the canonical secretory pathway that is transposed outside the parasite into the host cell, the first example of its kind in eukaryotic biology.
Insights
The study reveals how Plasmodium falciparum exports knob-associated histidine-rich protein (KAHRP) to cause malaria. Maurer's clefts are key to this process, acting as a novel secretory pathway outside the parasite.
Area of Science:
- Cell Biology
- Parasitology
- Molecular Biology
Background:
- Plasmodium falciparum infection causes malaria, a disease responsible for significant mortality.
- Microvascular sequestration, mediated by infected erythrocyte adherence to capillaries, is a critical virulence factor.
- Knob-associated histidine-rich protein (KAHRP) is essential for this cytoadherence mechanism.
Purpose of the Study:
- To elucidate the export pathway of KAHRP from the parasite to the erythrocyte.
- To identify sequence elements governing KAHRP trafficking.
- To characterize the role of Maurer's clefts in protein secretion.
Main Methods:
- Utilized green fluorescent protein (GFP) fusions to track KAHRP localization.
- Employed fluorescence recovery after photobleaching (FRAP) to analyze protein dynamics.
- Investigated the structural and functional aspects of Maurer's clefts.
Main Results:
- KAHRP is secreted via an intermediate depot before reaching the erythrocyte cytoplasm and knobs.
- Specific sequence elements were identified as crucial for distinct steps in KAHRP deployment.
- Maurer's clefts were demonstrated to be an extended secretory pathway outside the parasite, within the host cell.
Conclusions:
- The KAHRP export pathway is essential for Plasmodium falciparum virulence.
- Maurer's clefts represent a unique eukaryotic secretory system transposed into the host cell.
- Understanding this pathway offers potential targets for antimalarial interventions.
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