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Cell Microbiol. 2013 Jun;15(6):910-21. doi: 10.1111/cmi.12086. Epub 2012 Dec 28.

Ca(2+) -mediated exocytosis of subtilisin-like protease 1: a key step in egress of Plasmodium falciparum merozoites.

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1
Malaria Group, International Centre for Genetic Engineering and Biotechnology ICGEB, New Delhi, India.

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 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 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.

PMID:
23217145
DOI:
10.1111/cmi.12086
[Indexed for MEDLINE]
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