Plasmodium falciparum regulatory subunit of cAMP-dependent PKA and anion channel conductance.

TitlePlasmodium falciparum regulatory subunit of cAMP-dependent PKA and anion channel conductance.
Publication TypeJournal Article
Year of Publication2008
AuthorsMerckx A, Nivez M-P, Bouyer G, Alano P, Langsley G, Deitsch K, Thomas S, Doerig C, Egée S
JournalPLoS Pathog
Date Published2008 Feb 08
KeywordsAnimals, Anion Exchange Protein 1, Erythrocyte, Anions, Cell Membrane Permeability, Cells, Cultured, Cyclic AMP-Dependent Protein Kinases, Electrophysiology, Erythrocytes, Genes, Protozoan, Host-Parasite Interactions, Ion Channel Gating, Ion Channels, Membrane Potentials, Patch-Clamp Techniques, Plasmodium falciparum, Protozoan Proteins, Recombinant Proteins, Voltage-Dependent Anion Channels

Malaria symptoms occur during Plasmodium falciparum development into red blood cells. During this process, the parasites make substantial modifications to the host cell in order to facilitate nutrient uptake and aid in parasite metabolism. One significant alteration that is required for parasite development is the establishment of an anion channel, as part of the establishment of New Permeation Pathways (NPPs) in the red blood cell plasma membrane, and we have shown previously that one channel can be activated in uninfected cells by exogenous protein kinase A. Here, we present evidence that in P. falciparum-infected red blood cells, a cAMP pathway modulates anion conductance of the erythrocyte membrane. In patch-clamp experiments on infected erythrocytes, addition of recombinant PfPKA-R to the pipette in vitro, or overexpression of PfPKA-R in transgenic parasites lead to down-regulation of anion conductance. Moreover, this overexpressing PfPKA-R strain has a growth defect that can be restored by increasing the levels of intracellular cAMP. Our data demonstrate that the anion channel is indeed regulated by a cAMP-dependent pathway in P. falciparum-infected red blood cells. The discovery of a parasite regulatory pathway responsible for modulating anion channel activity in the membranes of P. falciparum-infected red blood cells represents an important insight into how parasites modify host cell permeation pathways. These findings may also provide an avenue for the development of new intervention strategies targeting this important anion channel and its regulation.

Alternate JournalPLoS Pathog
PubMed ID18248092
PubMed Central IDPMC2222956
Grant List / / Wellcome Trust / United Kingdom
R01 AI052390 / AI / NIAID NIH HHS / United States
AI 52390 / AI / NIAID NIH HHS / United States

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