PTP6 has been previously implicated in EMP1 trafficking and was shown to locate at the periphery of the Maurer’s clefts. Among the clusters was an uncharacterised protein, PF3D7_0301700, that interacts with the Maurer’s cleft resident protein, PfEMP1 trafficking protein 6 (PTP6). That work identified several key protein clusters that play an important role in EMP1 trafficking through the Maurer’s clefts. We recently reported a method for enrichment of Maurer’s clefts that enabled profiling of the protein composition and identification of protein networks within this organelle. Thus, it is possible that low complexity regions in exported Plasmodium proteins help regulate protein trafficking and host cell remodeling. Proteins with low complexity sequences have been shown to play critical roles in vesicle trafficking in other eukaryotes. For example, glutamine and asparagine repeats are present in about 30% of P. Īn interesting feature of exported Plasmodium proteins is that they are enriched in repetitive sequences with low sequence complexity. These EMP1-containing vesicles have been reported to associate with remodeled RBC actin filaments and membranous structures, called tethers, that decorate the Maurer’s clefts in the later stages of intraerythrocytic development. Of interest, coated electron-dense vesicles (EDVs) and uncoated vesicle-like structures have been observed in the host cytoplasm and have been shown to contain EMP1. The mechanisms controlling EMP1 insertion into the Maurer’s clefts and its subsequent forward trafficking and delivery to the RBC membrane remain unclear. Once exported across the PVM, EMP1 is thought to be trafficked across the RBC cytoplasm as a soluble, chaperoned complex and inserted into the membrane bilayer of the Maurer’s clefts-an intermediate trafficking compartment in the RBC cytoplasm. The trafficking of EMP1 and other virulence determinants beyond the confines of the parasite is mediated by the Plasmodium translocon of exported proteins (PTEX) that is present in the parasitophorous vacuole membrane (PVM), with help from a second complex termed the exported protein interacting complex (EPIC). falciparum erythrocyte membrane protein-1 (EMP1), which mediates binding of infected RBCs to endothelial ligands. The knob structure acts as an elevated platform at the RBC surface for presentation of the major virulence protein, P. One key modification is the assembly of ~90 nm diameter structures, called knobs, at the infected RBC surface. Maturation of the parasite inside the RBC is accompanied by striking changes in the surface topology of the infected RBC and a marked loss of cellular deformability. falciparum to maintain an infection and cause disease, is the invasion and remodelling of host red blood cells (RBCs). Plasmodium falciparum causes more than 200 million malaria infections every year, killing more than 600,000 people. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. MWAD and LT thank the National Health and Medical Research Council (1098992) ( ) for funding this work. All quantitative and qualitative microscopy data and analysis scripts are available from open-access Zenodo repositories (data DOI: 10.5281/zenodo.5146871 analysis scripts DOI: 10.5281/zenodo.5147885).įunding: LT is a Georgina Sweet, Australian Research Council Laureate Fellow (FL150100106) ( ). This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD027566. Received: AugAccepted: JPublished: August 5, 2022Ĭopyright: © 2022 Carmo et al. PLoS Pathog 18(8):Įditor: Isabelle Coppens, Johns Hopkins University Bloomberg School of Public Health, UNITED STATES (2022) Deletion of the Plasmodium falciparum exported protein PTP7 leads to Maurer’s clefts vesiculation, host cell remodeling defects, and loss of surface presentation of EMP1. Citation: Carmo OMS, Shami GJ, Cox D, Liu B, Blanch AJ, Tiash S, et al.

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