(A) Schematic representation of MICs and their processing pre-exocytosis (red) and post-exocytosis by ROM4/5 (light blue). (B) Immunoblots assessing the processing of the microneme proteins M2AP, MIC3, MIC6, AMA1 upon ASP3 knockdown. Catalase was used as loading control. (C) ASP3ty but not asp3ty-D299A can rescue the processing of MIC6 in absence of ASP3myc. (D), (E), (F) Immunoblots assessing the processing of the microneme proteins MIC5, TLN4 and PLP1 upon ASP3 knockdown. MIC5 was Ty-tagged at the endogenous locus in ASP3-iKD and transient plasmid transfection of epitope tagged TLN4 was used. (G) IFAs evaluating the localization of microneme proteins upon ASP3 depletion – M2AP, MIC6 and MIC3, co-localized with either MIC2 or AMA1. White arrowhead points to the pro form of M2AP. (H) Immunoblot analyses of ESA from ASP3ty-iKD parasites, +/−ATc, after 2% EtOH stimulation show impaired post-exocytosis cleavage of MIC2, M2AP and MIC4. (I) Schematic representation of microneme proteins and their putative processing post-exocytosis by SUB1. (J) Endogenously tagged SUB1 was localized in the microneme independently of ASP3. (K) Depletion of ASP3 showed impaired processing of SUB1in ESA analyses. TgSUB1 was detected using an antibody raised against PfSUB1. Black arrowheads represent pro and mature forms of the proteins.