PfPP1 function at an early step of parasite egress from erythrocytes. h PVM rupture at 45 hpi in pfpp1-iKO / PfEXP2-GFP parasites treated +/− Rapa at 30 hpi. Left: immunofluorescence images of parasites with intact or ruptured PVMs. Right: Proportion of infected cells exhibiting PVM rupture. For h–j, mean ± s.e.m.; n = 3 experiments; two-tailed t-test. In h–j, parasites were treated with E64 (50 μM) at 41 hpi; the completion of cytokinesis was assessed with the inner membrane complex marker PfMTIP or the parasite plasma membrane marker PfMSP1. Scale bars (h–j): 2 μm. i With +/− Rapa-treatment at 30 hpi in pfpp1-iKO parasites, quantification of PfSUB1 secretion from exonemal compartments (loss of punctate fluorescence in images at left), as in h. j Assessment of PfAMA1 secretion from micronemes, as in h and i. We used labeling by PfEXP2-GFP to test the requirement for PfPP1 in PVM rupture, finding that late induction of iKO blocks the process in virtually all parasites examined (h). We further used immunofluorescence analysis to assess PfSUB1 release required to initiate PVM rupture, finding that rapamycin treated pfpp1-iKO parasites fail to secrete the protease from exonemes stimulates a proteolytic cascade leading to sequential rupture of the PVM and the erythrocyte host membranes. We observed that discharge of micronemes is also blocked by pfpp1-iKO (j). Our findings indicate an essential function for PfPP1 at an early step of egress, following merozoite development but upstream of discharge of the specialized parasite organelles carrying proteases and other factors utilized for rupture of surrounding membranes.
Paul AS, Miliu A, Paulo JA, Goldberg JM, Bonilla AM, Berry L, Seveno M, Braun-Breton C, Kosber AL, Elsworth B, Arriola JSN, Lebrun M, Gygi SP, Lamarque MH, Duraisingh MT. Co-option of Plasmodium falciparum PP1 for egress from host erythrocytes. Nat Commun. 2020 11(1):3532.
Other associated proteins
|PF3D7_0507500||subtilisin-like protease 1|
|PF3D7_0930300||merozoite surface protein 1|
|PF3D7_1133400||apical membrane antigen 1|
|PF3D7_1246400||myosin a-tail interacting protein|
|PF3D7_1414400||serine/threonine protein phosphatase PP1|