Protein kinase A and C signalling in adult 'Schistosoma mansoni'

De Saram, Paulu Samramge Ranga (2011) Protein kinase A and C signalling in adult 'Schistosoma mansoni'. (MSc(R) thesis), Kingston University, .


'Schistosoma mansoni' is a medically important parasitic trematode that causes human schistosamiasis. Little is known about cell signalling in 'S. mansoni' and how signal transduction regulates fundamental aspects of schistosome biology. Protein kinases play a pivotal role in controlling cellular functions in vertebrates and invertebrates, with protein kinase C (PKC) and cAMP dependent kinase (PKA_ being crucial to the development/reproduction and survival of organisms. In this study, PKC and PKA activities were localized in intact adult 'S. mansoni' with the aid of commercially available anti-phospho PKC ([Beta]II-Ser660/-[Xi]Thr410) and anti-phospho PKA-C (PKA-CThr197) antibodies that detect phosphorylated (activated) forms of these kinases. Using laser scanning confocal microscopy, activated PKC was localized to the parasite tegument, oesophageal glands and musculature of adult worms, whereas activated PKA was localized to the tegument, ootype, uterus and musculature. PKA activity was also prominent on the posterior side of the egg and uterus, highlighting a potential role for PKA in muscle contraction to assist expulsion of eggs from the female. Furthermore, occasionally, striking PKA activation was seen within the nervous system of both male and female worms and this activity could be stimulated using the PKA activator forskolin which, by western blotting, was also shown to increase PKA phosphorylation. Moreover, PKA activity in the nervous system appeared to be increased during worm separation 'in vitro'. Finally, forskolin increased the frequency of gross muscular contractions in adult worms in a time- and dose-dependent manner. Taken together, these findings significantly increaseour knowledge of PKA and KC signalling in 'S. mansoni' and provide a framework to explore the activation of these pathways 'in situ' during schistosome development and host-parasite interactions.

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