Ca2+‐mediated exocytosis of subtilisin‐like protease 1: a key step in egress of Plasmodium falciparum merozoites |
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Authors: | Shalini Agarwal Maneesh Kumar Singh Swati Garg Chetan E Chitnis Shailja Singh |
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Institution: | Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), , New Delhi, India |
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Abstract: | Egress of Plasmodium falciparum merozoites from host erythrocytes is a critical step in multiplication of blood‐stage parasites. A cascade of proteolytic events plays a major role in degradation of membranes leading to egress of merozoites. However, the signals that regulate the temporal activation and/or secretion of proteases upon maturation of merozoites in intra‐erythrocytic schizonts remain unclear. Here, we have tested the role of intracellular Ca2+ in regulation of egress of P. falciparum merozoites from schizonts. A sharp rise in intracellular Ca2+ just before egress, observed by time‐lapse video microscopy, suggested a role for intracellular Ca2+ in this process. Chelation of intracellular Ca2+ with chelators such as BAPTA‐AM or inhibition of Ca2+ release from intracellular stores with a phospholipase C (PLC) inhibitor blocks merozoite egress. Interestingly, chelation of intracellular Ca2+ in schizonts was also found to block the discharge of a key protease PfSUB1 (subtilisin‐like protease 1) from exonemes of P. falciparum merozoites to parasitophorous vacuole (PV). This leads to inhibition of processing of PfSERA5 (serine repeat antigen 5) and a block in parasitophorous vacuolar membrane (PVM) rupture and merozoite egress. A complete understanding of the steps regulating egress of P. falciparum merozoites may provide novel targets for development of drugs that block egress and limit parasite growth. |
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