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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / physiology*
  • Cells, Cultured
  • Chelating Agents / pharmacology
  • Disease Models, Animal
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Erythrocyte Membrane / drug effects
  • Erythrocyte Membrane / parasitology
  • Erythrocytes / drug effects
  • Erythrocytes / parasitology*
  • Erythrocytes / pathology
  • Exocytosis / physiology*
  • Female
  • Malaria, Falciparum
  • Merozoites / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Video
  • Plasmodium falciparum / pathogenicity*
  • Plasmodium falciparum / physiology
  • Protozoan Proteins / physiology*
  • Subtilisins / physiology*


  • Chelating Agents
  • Protozoan Proteins
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Egtazic Acid
  • Subtilisins
  • subtilisin-like protease 1, Plasmodium falciparum
  • Calcium