A Plasmodium homolog of ER tubule-forming proteins is required for parasite virulence

Mol Microbiol. 2020 Sep;114(3):454-467. doi: 10.1111/mmi.14526. Epub 2020 Jun 19.


Reticulon and REEP family of proteins stabilize the high curvature of endoplasmic reticulum (ER) tubules. Plasmodium berghei Yop1 (PbYop1) is a REEP5 homolog in Plasmodium. Here, we characterize its function using a gene-knockout (Pbyop1∆). Pbyop1∆ asexual stage parasites display abnormal ER architecture and an enlarged digestive vacuole. The erythrocytic cycle of Pbyop1∆ parasites is severely attenuated and the incidence of experimental cerebral malaria is significantly decreased in Pbyop1∆-infected mice. Pbyop1∆ sporozoites have reduced speed, are slower to invade host cells but give rise to equal numbers of infected HepG2 cells, as WT sporozoites. We propose that PbYOP1's disruption may lead to defects in trafficking and secretion of a subset of proteins required for parasite development and invasion of erythrocytes. Furthermore, the maintenance of ER morphology in different parasite stages is likely to depend on different proteins.

Keywords: DP1; REEP; YOP1; endoplasmic reticulum; reticulon.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum / ultrastructure
  • Female
  • Gene Knockout Techniques
  • Genes, Protozoan
  • Hep G2 Cells
  • Humans
  • Malaria / pathology*
  • Malaria / transmission
  • Male
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission
  • Movement
  • Plasmodium berghei / genetics*
  • Plasmodium berghei / metabolism*
  • Plasmodium berghei / ultrastructure
  • Protein Transport
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Rats
  • Rats, Wistar
  • Sporozoites / metabolism
  • Virulence


  • Membrane Transport Proteins
  • Protozoan Proteins