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

Scientific Reports
Elizabeth S ZuccalaJake Baum

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.

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Citations

Aug 31, 2016·The Journal of Cell Biology·Isabelle Tardieux, Jake Baum
May 24, 2016·Molecular and Biochemical Parasitology·Teresa Gil CarvalhoChristian Doerig
Mar 18, 2017·Current Opinion in Hematology·Aditi AlagananChetan E Chitnis
Mar 11, 2017·Cell Host & Microbe·Jake BaumDavid T Riglar
Oct 21, 2017·Blood·Patrick G Gallagher
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Sep 5, 2017·Nature Reviews. Microbiology·Karine FrénalDominique Soldati-Favre
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Sep 19, 2019·Science Signaling·Gholamreza Haqshenas, Christian Doerig
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Jul 25, 2019·Nature Communications·Julien Robert-PaganinAnne Houdusse
Apr 5, 2017·Proceedings of the National Academy of Sciences of the United States of America·Marion KochJake Baum
Feb 21, 2021·Nature Communications·Elya DekelNeta Regev-Rudzki
Apr 4, 2021·International Journal of Molecular Sciences·Vassilis L TzounakasMarianna H Antonelou

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Methods Mentioned

BETA
flow cytometry
proteomic assay
Protein Assay

Software Mentioned

Excel
Prism
SEQUEST
Scaffold
SoftWoRx
Xcalibur
EditSeq
NetPhosK
DNASTAR Lasergene
Proteome

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