CaMKII regulates neuromuscular activity and survival of the human blood fluke Schistosoma mansoni

Natasha L. Hirst, Scott P. Lawton, Anthony J. Walker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Calcium/calmodulin dependant protein kinase II (CaMKII), an important transducer of Ca2+ signals, orchestrates multiple cellular functions in animals. Here we investigated the importance of CaMKII to Schistosoma mansoni, a blood parasite that causes human schistosomiasis. We demonstrate that phosphorylated (activated) CaMKII is present in cercariae, schistosomula and adult worms, and show that striking activation occurs in the nervous tissue of these parasite life-stages; CaMKII was also activated in the tegument and muscles of adult worms and the vitellaria of females. Exposure of worms to the anti-schistosomal drug praziquantel (PZQ) induced significant CaMKII activation and depletion of CaMKII protein/activation in adult worms resulted in hypokinesia, reduced vitality and death. At medium confidence (global score ≥ 0.40), S. mansoni CaMKII was predicted to interact with 51 proteins, with many containing CaMKII phosphorylation sites and nine mapped to phosphoproteome data including sites within a ryanodine receptor. The CaMKII network was functionally enriched with mitogen-activated protein kinase, Wnt, and notch pathways, and ion-transport and voltage-dependent channel protein domains. Collectively, these data highlight the intricacies of CaMKII signalling in S. mansoni, show CaMKII to be an active player in the PZQ-mediated response of schistosomes and highlight CaMKII as a possible target for the development of novel anti-schistosome therapeutics.
Original languageEnglish
Article number19831
JournalScientific Reports
Volume12
Issue number1
Early online date18 Nov 2022
DOIs
Publication statusPrint publication - Dec 2022

Keywords

  • Praziquantel/pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
  • Schistosoma mansoni
  • Humans
  • Animals
  • Anthelmintics/pharmacology
  • Female
  • Calcium Signaling

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