title: Plasmodiumfalciparum infection induces dynamic changes in the erythrocyte phospho-proteome.
abstract: 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.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR 8227, Comparative Physiology of Erythrocytes, Station Biologique de Roscoff, CS 90074 Roscoff, France; Centre National de la Recherche Scientifique, UMR 8227, Comparative Physiology of Erythrocytes, Station Biologique de Roscoff, CS 90074 Roscoff, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bouyer
authors.affiliation: Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médécine, Université Paris Descartes, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France; Institut Cochin, INSERM U1016, CNRS UMR, 8104 Paris, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Reininger
authors.affiliation: Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médécine, Université Paris Descartes, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France; Institut Cochin, INSERM U1016, CNRS UMR, 8104 Paris, France.
authors.forename: Ghania
authors.initials: G
authors.lastname: Ramdani
authors.affiliation: School of Biomedical and Healthcare Sciences, Plymouth University, Drake Circus, Plymouth, Devon, UK.
authors.forename: Lee
authors.initials: L
authors.lastname: D Phillips
authors.affiliation: School of Biomedical and Healthcare Sciences, Plymouth University, Drake Circus, Plymouth, Devon, UK; Systems Biology Centre, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth University, Drake Circus, Plymouth, Devon, UK.
authors.forename: Vikram
authors.initials: V
authors.lastname: Sharma
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR 8227, Comparative Physiology of Erythrocytes, Station Biologique de Roscoff, CS 90074 Roscoff, France; Centre National de la Recherche Scientifique, UMR 8227, Comparative Physiology of Erythrocytes, Station Biologique de Roscoff, CS 90074 Roscoff, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Egee
authors.affiliation: Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médécine, Université Paris Descartes, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France; Institut Cochin, INSERM U1016, CNRS UMR, 8104 Paris, France.
authors.forename: Gordon
authors.initials: G
authors.lastname: Langsley
authors.affiliation: School of Biomedical and Healthcare Sciences, Plymouth University, Drake Circus, Plymouth, Devon, UK.
authors.forename: Edwin
authors.initials: E
authors.lastname: Lasonder
mesh_terms: D000595:Amino Acid Sequence; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis / Q000378:metabolism; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism / Q000469:parasitology; D004912:Erythrocytes / Q000737:chemistry / Q000378:metabolism / Q000469:parasitology*; D051272:Glucose Transporter Type 1 / Q000032:analysis / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000378:metabolism*; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000502:physiology*; D020543:Proteome / Q000032:analysis / Q000378:metabolism*
chemical_list: D051272:Glucose Transporter Type 1; D020543:Proteome; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Cytoskeleton; Erythrocyte; GLUT-1; P.falciparum; Protein phosphorylation; cAMP/protein kinase A