Deletion of the Plasmodium falciparum exported protein PTP7 leads to Maurer's clefts vesiculation, host cell remodeling defects, and loss of surface presentation of EMP1

PLoS Pathog. 2022 Aug 5;18(8):e1009882. doi: 10.1371/journal.ppat.1009882. eCollection 2022 Aug.

Abstract

Presentation of the variant antigen, Plasmodium falciparum erythrocyte membrane protein 1 (EMP1), at knob-like protrusions on the surface of infected red blood cells, underpins the parasite's pathogenicity. Here we describe a protein PF3D7_0301700 (PTP7), that functions at the nexus between the intermediate trafficking organelle, the Maurer's cleft, and the infected red blood cell surface. Genetic disruption of PTP7 leads to accumulation of vesicles at the Maurer's clefts, grossly aberrant knob morphology, and failure to deliver EMP1 to the red blood cell surface. We show that an expanded low complexity sequence in the C-terminal region of PTP7, identified only in the Laverania clade of Plasmodium, is critical for efficient virulence protein trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Erythrocyte Membrane / metabolism
  • Erythrocytes / metabolism
  • Organelles / metabolism
  • Plasmodium falciparum* / metabolism
  • Protein Transport
  • Protozoan Proteins* / genetics
  • Protozoan Proteins* / metabolism

Substances

  • Protozoan Proteins

Grants and funding

LT is a Georgina Sweet, Australian Research Council Laureate Fellow (FL150100106) (http://www.arc.gov.au). MWAD and LT thank the National Health and Medical Research Council (1098992) (https://www.nhmrc.gov.au) for funding this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.