The PV is generated through invagination of the erythrocyte membrane during invasion. Discharge of the rhoptry and dense granule secretory organelles during and immediately after invasion rapidly establishes transport activities at the PVM. This is followed by a major wave of protein export during the early stages of intraerythrocytic development to remodel the host cell. During this time, the parasite exomembrane system is also generated, including TVN extensions of the PV thought to provide greater surface area for nutrient uptake and Maurer’s clefts, which serve as trafficking platforms for parasite exported effectors en route to the host membrane. Near the end of this period, a major increase in host membrane permeability is facilitated by activation of NPPs including PSAC. In addition to these changes in erythrocyte permeability, key host modifications include cytoskeletal rigidification and the formation of raised knobs on the erythrocyte surface for display of adhesins that mediate iRBC sequestration and immune evasion. In P. falciparum, the responsible variant surface antigens include PfEMP1, the RIFINs, and the STEVORs, each encoded by large, multigene families. Endocytic uptake of hemoglobin-rich host cytosol and degradation in the digestive vacuole liberates amino acids to support parasite metabolism and frees space for expansive growth within the erythrocyte. ER, endoplasmic reticulum; iRBC, infected red blood cell; NPPs, new permeability pathways; PfEMP1, P. falciparum erythrocyte membrane protein 1; PSAC, Plasmodial surface anion channel; PV, parasitophorous vacuole; PVM, PV membrane; RIFIN, repetitive interspersed family protein; STEVOR, sub-telomeric variable open reading frame protein; TVN, tubulovesicular network. Beck JR, Ho CM. Transport mechanisms at the malaria parasite-host cell interface. PLoS Pathog. 2021 17(4):e1009394. PMID: 33793667

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