Protein kinase A signalling in Schistosoma mansoni cercariae and schistosomules

Natasha L Hirst, Scott P Lawton, Anthony J Walker

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Cyclic AMP (cAMP)-dependent protein kinase/protein kinase A regulates multiple processes in eukaryotes by phosphorylating diverse cellular substrates, including metabolic and signalling enzymes, ion channels and transcription factors. Here we provide insight into protein kinase A signalling in cercariae and 24h in vitro cultured somules of the blood parasite, Schistosoma mansoni, which causes human intestinal schistosomiasis. Functional mapping of activated protein kinase A using anti-phospho protein kinase A antibodies and confocal laser scanning microscopy revealed activated protein kinase A in the central and peripheral nervous system, oral-tip sensory papillae, oesophagus and excretory system of intact cercariae. Cultured 24h somules, which biologically represent the skin-resident stage of the parasite, exhibited similar activation patterns in oesophageal and nerve tissues but also displayed striking activation at the tegument and activation in a region resembling the germinal 'stem' cell cluster. The adenylyl cyclase activator, forskolin, stimulated somule protein kinase A activation and produced a hyperkinesia phenotype. The biogenic amines, serotonin and dopamine known to be present in skin also induced protein kinase A activation in somules, whereas neuropeptide Y or [Leu(31),Pro(34)]-neuropeptide Y attenuated protein kinase A activation. However, neuropeptide Y did not block the forskolin-induced somule hyperkinesia. Bioinformatic investigation of potential protein associations revealed 193 medium confidence and 59 high confidence protein kinase A interacting partners in S. mansoni, many of which possess putative protein kinase A phosphorylation sites. These data provide valuable insight into the intricacies of protein kinase A signalling in S. mansoni and a framework for further physiological investigations into the roles of protein kinase A in schistosomes, particularly in the context of interactions between the parasite and the host.

Original languageEnglish
Pages (from-to)425-37
Number of pages13
JournalInternational Journal for Parasitology
Volume46
Issue number7
Early online date14 Jan 2016
DOIs
Publication statusPrint publication - Jun 2016
Externally publishedYes

Keywords

  • Adjuvants, Immunologic/pharmacology
  • Amino Acid Sequence
  • Animals
  • Antibodies, Helminth/immunology
  • Biomphalaria
  • Blotting, Western
  • Colforsin/pharmacology
  • Cyclic AMP-Dependent Protein Kinases/chemistry
  • Dopamine/pharmacology
  • Dopamine Agents/pharmacology
  • Enzyme Activation/drug effects
  • Humans
  • Neuropeptide Y/pharmacology
  • Schistosoma mansoni/drug effects
  • Sequence Alignment
  • Serotonin/pharmacology
  • Serotonin Receptor Agonists/pharmacology
  • Signal Transduction

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