The Plasmodium falciparum parasitophorous vacuole protein P113 interacts with the parasite protein export machinery and maintains normal vacuole architecture

Mol Microbiol. 2022 May;117(5):1245-1262. doi: 10.1111/mmi.14904. Epub 2022 Apr 25.

Abstract

Infection with Plasmodium falciparum parasites results in approximately 627,000 deaths from malaria annually. Key to the parasite's success is their ability to invade and subsequently grow within human erythrocytes. Parasite proteins involved in parasite invasion and proliferation are therefore intrinsically of great interest, as targeting these proteins could provide novel means of therapeutic intervention. One such protein is P113 which has been reported to be both an invasion protein and an intracellular protein located within the parasitophorous vacuole (PV). The PV is delimited by a membrane (PVM) across which a plethora of parasite-specific proteins are exported via the Plasmodium Translocon of Exported proteins (PTEX) into the erythrocyte to enact various immune evasion functions. To better understand the role of P113 we isolated its binding partners from in vitro cultures of P. falciparum. We detected interactions with the protein export machinery (PTEX and exported protein-interacting complex) and a variety of proteins that either transit through the PV or reside on the parasite plasma membrane. Genetic knockdown or partial deletion of P113 did not significantly reduce parasite growth or protein export but did disrupt the morphology of the PVM, suggesting that P113 may play a role in maintaining normal PVM architecture.

Keywords: Plasmodium falciparum; blebs; erythrocyte; invasion; protein trafficking; vacuole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Erythrocytes / parasitology
  • Humans
  • Malaria, Falciparum* / parasitology
  • Parasites* / metabolism
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / metabolism
  • Protein Transport / genetics
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Vacuoles / metabolism

Substances

  • Protozoan Proteins