Plasmodium falciparum regulatory subunit of cAMP-dependent PKA and anion channel conductance. Academic Article uri icon

Overview

MeSH

  • Animals
  • Anions
  • Cell Membrane Permeability
  • Cells, Cultured
  • Electrophysiology
  • Genes, Protozoan
  • Host-Parasite Interactions
  • Ion Channel Gating
  • Ion Channels
  • Membrane Potentials
  • Patch-Clamp Techniques
  • Recombinant Proteins

MeSH Major

  • Anion Exchange Protein 1, Erythrocyte
  • Cyclic AMP-Dependent Protein Kinases
  • Erythrocytes
  • Plasmodium falciparum
  • Protozoan Proteins
  • Voltage-Dependent Anion Channels

abstract

  • 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.

publication date

  • February 8, 2008

has subject area

  • Animals
  • 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

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2222956

Digital Object Identifier (DOI)

  • 10.1371/journal.ppat.0040019

PubMed ID

  • 18248092

Additional Document Info

start page

  • e19

volume

  • 4

number

  • 2