Plasmodium falciparum Regulatory Subunit of cAMP-Dependent PKA and Anion Channel Conductance

PLoS Pathogens

Serge Thomas¹  Anaïs Merckx²  Stéphane Egée²  Guillaume Bouyer²  Marie-Paule Nivez³  Kirk Deitsch³  Gordon Langsley⁴  Pietro Alano⁵  Christian Doerig⁵ 

[1] Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, United States of America;INSERM U609, Wellcome Center for Molecular Parasitology, Glasgow Biomedical Research Centre, Glasgow, Scotland, United Kingdom;Institut Cochin, INSERM U567, Université Paris Descartes, CNRS (UMR 8104), Paris, France;Instituto Superiore de Sanita, Rome, Italy;Université Pierre et Marie Curie – CNRS UMR 7150, Roscoff, France

关键词: Parasitic diseases;    Red blood cells;    Cell membranes;    Anions;    Plasmodium;    Malarial parasites;    Parasitic cell cycles;    Pipettes;   

DOI  :  10.1371/journal.ppat.0040019

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY