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 Ca2+ levels via induction of an Epac pathway and demonstrate that increases in both cAMP and Ca2+ 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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Dawn A,Singh S,More KR,Siddiqui FA,Pachikara N,Ramdani G,Langsley G,Chitnis CE

doi

10.1371/journal.ppat.1004520

subject

Has Abstract

pub_date

2014-12-18 00:00:00

pages

e1004520

issue

12

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-14-00038

journal_volume

10

pub_type

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