The Central Role of cAMP in Regulating Plasmodium falciparum Merozoite Invasion of Human Erythrocytes - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles PLoS Pathogens Year : 2014

The Central Role of cAMP in Regulating Plasmodium falciparum Merozoite Invasion of Human Erythrocytes

Abstract

All pathogenesis and death associated with Plasmodium falciparum malaria is due to parasite-infected erythrocytes. Invasion of erythrocytes by P. falciparum merozoites requires specific interactions between host receptors and parasite ligands that are localized in apical organelles called micronemes. Here, we identify cAMP as a key regulator that triggers the timely secretion of microneme proteins enabling receptor-engagement and invasion. We demonstrate that exposure of merozoites to a low K + environment, typical of blood plasma, activates a bicarbonate-sensitive cytoplasmic adenylyl cyclase to raise cytosolic cAMP levels and activate protein kinase A, which regulates microneme secretion. We also show that cAMP regulates merozoite cytosolic Ca 2+ levels via induction of an Epac pathway and demonstrate that increases in both cAMP and Ca 2+ are essential to trigger microneme secretion. Our identification of the different elements in cAMP-dependent signaling pathways that regulate microneme secretion during invasion provides novel targets to inhibit blood stage parasite growth and prevent malaria.
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inserm-01103410 , version 1 (14-01-2015)

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Amrita Dawn, Shailja Singh, Kunal R More, Faiza Amber Siddiqui, Niseema Pachikara, et al.. The Central Role of cAMP in Regulating Plasmodium falciparum Merozoite Invasion of Human Erythrocytes. PLoS Pathogens, 2014, 10 (12), pp.e1004520. ⟨10.1371/journal.ppat.1004520⟩. ⟨inserm-01103410⟩
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