Open AccessCa 2+ ‐mediated exocytosis of subtilisin‐like protease 1: a key step in egress of P lasmodium falciparum merozoites
Author(s) -
Agarwal Shalini,
Singh Maneesh Kumar,
Garg Swati,
Chitnis Chetan E.,
Singh Shailja
Publication year - 2013
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12086
Subject(s) - plasmodium falciparum , intracellular , biology , proteases , rhoptry , microbiology and biotechnology , protease , vacuole , secretion , serine protease , exocytosis , intracellular parasite , biochemistry , apicomplexa , enzyme , immunology , cytoplasm , malaria
Summary Egress of P lasmodium 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 Ca 2+ in regulation of egress of P . falciparum merozoites from schizonts. A sharp rise in intracellular Ca 2+ just before egress, observed by time‐lapse video microscopy, suggested a role for intracellular Ca 2+ in this process. Chelation of intracellular Ca 2+ with chelators such as BAPTA ‐ AM or inhibition of Ca 2+ release from intracellular stores with a phospholipase C ( PLC ) inhibitor blocks merozoite egress. Interestingly, chelation of intracellular Ca 2+ in schizonts was also found to block the discharge of a key protease PfSUB 1 (subtilisin‐like protease 1) from exonemes of P . falciparum merozoites to parasitophorous vacuole ( PV ). This leads to inhibition of processing of PfSERA 5 (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.