Plasmodiumfalciparum infection induces dynamic changes in the erythrocyte phospho-proteome

Blood Cells Mol Dis. 2016 May:58:35-44. doi: 10.1016/j.bcmd.2016.02.001. Epub 2016 Feb 13.


The phosphorylation status of red blood cell proteins is strongly altered during the infection by the malaria parasite Plasmodium falciparum. We identify the key phosphorylation events that occur in the erythrocyte membrane and cytoskeleton during infection, by a comparative analysis of global phospho-proteome screens between infected (obtained at schizont stage) and uninfected RBCs. The meta-analysis of reported mass spectrometry studies revealed a novel compendium of 495 phosphorylation sites in 182 human proteins with regulatory roles in red cell morphology and stability, with about 25% of these sites specific to infected cells. A phosphorylation motif analysis detected 7 unique motifs that were largely mapped to kinase consensus sequences of casein kinase II and of protein kinase A/protein kinase C. This analysis highlighted prominent roles for PKA/PKC involving 78 phosphorylation sites. We then compared the phosphorylation status of PKA (PKC) specific sites in adducin, dematin, Band 3 and GLUT-1 in uninfected RBC stimulated or not by cAMP to their phosphorylation status in iRBC. We showed cAMP-induced phosphorylation of adducin S59 by immunoblotting and we were able to demonstrate parasite-induced phosphorylation for adducin S726, Band 3 and GLUT-1, corroborating the protein phosphorylation status in our erythrocyte phosphorylation site compendium.

Keywords: Cytoskeleton; Erythrocyte; GLUT-1; P.falciparum; Protein phosphorylation; cAMP/protein kinase A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / analysis
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cytoskeleton / chemistry
  • Cytoskeleton / metabolism
  • Cytoskeleton / parasitology
  • Erythrocytes / chemistry
  • Erythrocytes / metabolism
  • Erythrocytes / parasitology*
  • Glucose Transporter Type 1 / analysis
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Malaria, Falciparum / metabolism*
  • Phosphorylation
  • Plasmodium falciparum / physiology*
  • Proteome / analysis
  • Proteome / metabolism*


  • Glucose Transporter Type 1
  • Proteome
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases