Figure 2. Active, intracellular apicomplexan infection and transport across the PVM.

a. Schematic of apicomplexan with characteristic apical organelles as shown, N Nucleus. b Plasmodium falciparum infection of the red cell, establishes the parasitophorous vacuolar member (PVM) surrounding the vacuole (PV) in which the parasite bounded by the parasite plasma membrane (PPM) resides. Other than the apicoplast (not shown) the remaining apical organelles are lost, while membrane structures become prominent in the erythrocyte. Proteins made in the ER (which contains the lipid PI3P and the protease Plasmepsin V, PMV) with HT/PEXEL signal or as PNEPs are exported out across the PPM and PVM through the PTEX (filled blue circle and arrow). Parasite encoded adhesin PfEMP1 family proteins are concentrated and displayed on ‘knobs’ that enable binding to endothelial tissue enabling tissue sequestration, severe malaria disease and death. c. Tachyzoites (causing active Toxoplasma gondii infection) replicate within the PVM which becomes associated with host mitochondria and ER. Dense granule proteins (purple filled circles) are released into the parasitophorous vacuolar (PV) space inducing formation of the membranous nanotubular network (MNN). Dense granule proteins are also detected at the PVM (brown filled circles), where the proteins GRA17 (red) and GRA23 (green) mediate permeation of small molecules across the PVM. Dense granule proteins (yellow) are also detected in host nucleus (grey) where they modulate the host response. T. gondii Asp5 is a Golgi-localized aspartic protease that cleaves an N terminal HT/PEXEL like motif on substrates that include dense granule proteins delivered to the host cytoplasm and nucleus (deep and light yellow). Blue arrow indicates protein translocation across the PVM for which the signals and transport apparatus remain unknown.