Quantitative phospho-proteomics reveals the Plasmodium merozoite triggers pre-invasion host kinase modification of the red cell cytoskeleton

Elizabeth S Zuccala, Timothy J Satchwell, Fiona Angrisano, Yan Hong Tan, Marieangela C Wilson, Kate J Heesom, Jake Baum

Research output: Contribution to journalArticle (Academic Journal)peer-review

30 Citations (Scopus)
298 Downloads (Pure)

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.

Original languageEnglish
Article number19766
Number of pages16
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 2 Feb 2016

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