title: Protein kinase A signalling in Schistosoma mansoni cercariae and schistosomules.
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.
authors.affiliation: Molecular Parasitology Laboratory, School of Life Sciences, Kingston University, Kingston upon Thames, Surrey KT1 2EE, UK.
authors.forename: Natasha L
authors.initials: NL
authors.lastname: Hirst
authors.affiliation: Molecular Parasitology Laboratory, School of Life Sciences, Kingston University, Kingston upon Thames, Surrey KT1 2EE, UK.
authors.forename: Scott P
authors.initials: SP
authors.lastname: Lawton
authors.affiliation: Molecular Parasitology Laboratory, School of Life Sciences, Kingston University, Kingston upon Thames, Surrey KT1 2EE, UK. Electronic address: t.walker@kingston.ac.uk.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Walker
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D001700:Biomphalaria; D015153:Blotting, Western; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009478:Neuropeptide Y / Q000494:pharmacology; D012550:Schistosoma mansoni / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development / Q000502:physiology; D016415:Sequence Alignment; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D000276:Adjuvants, Immunologic; D000909:Antibodies, Helminth; D015259:Dopamine Agents; D009478:Neuropeptide Y; D017366:Serotonin Receptor Agonists; D005576:Colforsin; D012701:Serotonin; D017868:Cyclic AMP-Dependent Protein Kinases; D004298:Dopamine
keywords: Cercariae; Cyclic AMP (cAMP)-dependent protein kinase/protein kinase A; Dopamine; Neuropeptide Y; STRING; Schistosomule; Serotonin (5-HT)