Protein trafficking in Plasmodium falciparum-infected red cells and impact of the expansion of exported protein families

Abstract

S U M M A R YErythrocytes are extensively remodelled by the malaria parasite following invasion of the cell. Plasmodium falciparum encodes numerous virulence-associated and host-cell remodelling proteins that are trafficked to the cytoplasm, the cell membrane and the surface of the infected erythrocyte. The export of soluble proteins relies on a sequence directing entry into the secretory pathways in addition to an export signal. The export signal consisting of five amino acids is termed the Plasmodium export element (PEXEL) or the vacuole transport signal (VTS). Genome mining studies have revealed that PEXEL/VTS carrying protein families have expanded dramatically in P. falciparum compared with other malaria parasite species, possibly due to lineage-specific expansion linked to the unique requirements of P. falciparum for host-cell remodelling. The functional characterization of such genes and gene families may reveal potential drug targets that could inhibit protein trafficking in infected erythrocytes. This review highlights some of the recent advances and key knowledge gaps in protein trafficking pathways in P. falciparum-infected red cells and speculates on the impact of exported gene families in the trafficking pathway.

The transcriptome of circulating sexually committed Plasmodium falciparum ring stage parasites forecasts malaria transmission potential

“…This domain was first identified in P. knowlesi and thought to be exposed on the RBC surface. The surfins also have a noncanonical export signal 35 , consistent with transport to the RBC and, possibly, exposure on the iRBC surface. Together, these characteristics suggest that SURFIN 1.2 and 13.1 could be involved in modifications of the gc-ring-infected erythrocyte that may provide the first step toward sequestration; however, this needs to be investigated further.…”

NK-, NKT- and CD8-Derived IFNγ Drives Myeloid Cell Activation and Erythrophagocytosis, Resulting in Trypanosomosis-Associated Acute Anemia

“…Trypanosome infections are known to induce inflammation and inflammation-associated pathology [6,8–10,12–16]. In murine T .…”

“…Early during the course of infection, myeloid cells get activated by released parasite components such as soluble variant surface glycoproteins (sVSG) and DNA [1–7]. This gives rise to a type 1 cytokine storm which is critical for resistance [6,8–11], but is also associated with pathology development [12–16]. Indeed, coinciding with the acute inflammatory reaction, acute anemia develops, as witnessed by a 50% reduction in circulating red blood cells (RBC) within two days following peak parasitemia.…”

The Cytoplasmic Region of <i>Plasmodium falciparum</i> SURFIN_4.2 Is Required for Transport from Maurer’s Clefts to the Red Blood Cell Surface

“…The pathology of the parasite derives from the lifecycle stage which targets red blood cells (RBC) and replicates inside of the parasitophorous vacuole membrane (PVM) which is generated during invasion. After completion of the invasion process the parasite begins export of proteins to the RBC cytosol across the PVM [ 2 ]. These parasite-encoded exported proteins are classified into two types; specifically, 1) those containing basically N-terminal hydrophobic endoplasmic reticulum signal peptide region followed by a pentameric amino acids motif called a Plasmodium export element (PEXEL) and 2) those without PEXEL motif (PEXEL negative exported proteins, PNEPs), for which most are transmembrane proteins.…”