SUB1 is required for PVM disruption and RBCM poration, whereas the ΔSERA6 phenotype mimics egress arrest with the cysteine protease
inhibitor E64. a, Stills from simultaneous time-lapse DIC and fluorescence microscopic examination of typical control WT, ΔSUB1 and ΔSERA6 schizonts at the indicated intervals following removal of the egress inhibitor C2. PVM rupture and RBCM poration (indicated by access of phalloidin to the host RBC cytoskeleton) occurs in the ΔSERA6 parasites but not in the ΔSUB1 parasites, while RBCM rupture does not occur in either mutant. Scale bar, 10 μ m.
b, TEM micrographs of an arrested ΔSUB1 schizont and a C2-arrested control cell, showing that the trapped merozoites are surrounded in both cases by an intact PVM and RBCM. Knob structures characteristic of the parasite-infected RBCM6 are indicated on its outer surface (arrow heads). The black dots are gold fiducials added for tomography. Scale bars, 500 nm. c, Scanning electron microscopy images of ΔSERA6 schizonts before and 30 min following C2 removal, showing collapse of the RBCM around the intracellular merozoites in the washed sample. Scale bar, 5 μ m. d, TEM micrographs of an arrested
ΔSERA6 schizont and an E64-arrested control cell, showing in both remnants of ruptured PVM (asterisks) adjacent to the trapped merozoites. Knobs are highlighted as above (arrow heads). Scale bars, 500 nm. All experiments were repeated twice, with reproducible results. WGA, wheat germ agglutinin.
Thomas JA, Tan MYS, Bisson C, Borg A, Umrekar TR, Hackett F, Hale VL, Vizcay-Barrena G, Fleck RA, Snijders AP, Saibil HR, Blackman MJ. A protease cascade regulates release of the human malaria parasite Plasmodium falciparum from host red blood cells. Nat Microbiol. 2018 Feb 19.. [Epub ahead of print]
Other associated proteins
PFID | Formal Annotation |
---|---|
PF3D7_0507500 | subtilisin-like protease 1 |