title: Quantitative phospho-proteomics reveals the Plasmodium merozoite triggers pre-invasion host kinase modification of the red cell cytoskeleton.
abstract: The invasive blood-stage malaria parasite - the merozoite - induces rapid morphological changes to the target erythrocyte during entry. However, evidence for active molecular changes in the host cell that accompany merozoite invasion is lacking. Here, we use invasion inhibition assays, erythrocyte resealing and high-definition imaging to explore red cell responses during invasion. We show that although merozoite entry does not involve erythrocyte actin reorganisation, it does require ATP to complete the process. Towards dissecting the ATP requirement, we present an in depth quantitative phospho-proteomic analysis of the erythrocyte during each stage of invasion. Specifically, we demonstrate extensive increased phosphorylation of erythrocyte proteins on merozoite attachment, including modification of the cytoskeletal proteins beta-spectrin and PIEZO1. The association with merozoite contact but not active entry demonstrates that parasite-dependent phosphorylation is mediated by host-cell kinase activity. This provides the first evidence that the erythrocyte is stimulated to respond to early invasion events through molecular changes in its membrane architecture.
authors.affiliation: Division of Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Zuccala
authors.affiliation: School of Biochemistry, University of Bristol, Bristol, United Kingdom.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Satchwell
authors.affiliation: Division of Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: Angrisano
authors.affiliation: Division of Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Yan Hong
authors.initials: YH
authors.lastname: Tan
authors.affiliation: School of Biochemistry, University of Bristol, Bristol, United Kingdom.
authors.forename: Marieangela C
authors.initials: MC
authors.lastname: Wilson
authors.affiliation: School of Biochemistry, University of Bristol, Bristol, United Kingdom.
authors.forename: Kate J
authors.initials: KJ
authors.lastname: Heesom
authors.affiliation: Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom.
authors.forename: Jake
authors.initials: J
authors.lastname: Baum
mesh_terms: D003599:Cytoskeleton / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D052940:Merozoites / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D040901:Proteomics; D013049:Spectrin / Q000378:metabolism
chemical_list: D007473:Ion Channels; C515204:PIEZO1 protein, human; D010750:Phosphoproteins; D013049:Spectrin; D011494:Protein Kinases
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