RT Journal Article SR Electronic T1 Virulence determinant, PTP7, controls vesicle budding from the Maurer’s clefts, adhesin protein trafficking and host cell remodeling in Plasmodium falciparum JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.08.12.456062 DO 10.1101/2021.08.12.456062 A1 Olivia M. S. Carmo A1 Gerald J. Shami A1 Dezerae Cox A1 Boyin Liu A1 Adam J. Blanch A1 Snigdha Tiash A1 Leann Tilley A1 Matthew W.A. Dixon YR 2021 UL http://biorxiv.org/content/early/2021/08/12/2021.08.12.456062.abstract AB 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 P. falciparum malaria 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, found only in the Laverania clade of Plasmodium, is critical for efficient virulence protein trafficking.Author Summary We describe a malaria parasite protein involved in virulence factor trafficking (PTP7) that moves between different compartments in the host red blood cell cytoplasm in a stage-dependent manner. Upon disruption of the PTP7 locus, the Maurer’s cleft trafficking compartments become decorated with vesicles; the knobby protrusions on the host red blood cell surface are depleted and distorted; and trafficking of the virulence protein, EMP1, to the host red blood cell surface is ablated. We provide evidence that a region of PTP7 with low sequence complexity plays an important role in driving fission of vesicles from the Maurer’s clefts.Competing Interest StatementThe authors have declared no competing interest.