Uncovering Notch pathway in the parasitic flatworm Schistosoma mansoni

Abstract

Several signaling molecules that govern development in higher animals have been identified in the parasite Schistosoma mansoni, including the transforming growth factor β, protein tyrosine kinases, nuclear hormone receptors, among others. The Notch pathway is a highly conserved signaling mechanism which is involved in a wide variety of developmental processes including embryogenesis and oogenesis in worms and flies. Here we aimed to provide the molecular reconstitution of the Notch pathway in S. mansoni using the available transcriptome and genome databases. Our results also revealed the presence of the transcripts coded for SmNotch, SmSu(H), SmHes, and the gamma-secretase complex (SmNicastrin, SmAph-1, and SmPen-2), throughout all the life stages analyzed. Besides, it was observed that the viability and separation of adult worm pairs were not affected by treatment with N-[N(3,5)-difluorophenacetyl)-L-Alanyl]-S-phenylglycine t-butyl ester (DAPT), a Notch pathway inhibitor. Moreover, DAPT treatment decreased the production of phenotypically normal eggs and arrested their development in culture. Our results also showed a significant decrease in SmHes transcript levels in both adult worms and eggs treated with DAPT. These results provide, for the first time, functional validation of the Notch pathway in S. mansoni and suggest its involvement in parasite oogenesis and embryogenesis. Given the complexity of the Notch pathway, further experiments shall highlight the full repertoire of Notch-mediated cellular processes throughout the S. mansoni life cycle.

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

“…For example, Smp_026510 (MEK2) is a putative target of CaMKII and this protein is an upstream regulator of ERK, a protein that we found to be phosphorylated by PZQ exposure and to profoundly affect S. mansoni motility, pairing, attachment, and egg release 38 . Moreover, the notch pathway has been found to regulate oogenesis and embryogenesis in S. mansoni 56 . Given that Wnt and notch are central to organism development, it is possible that CaMKII interactions with MAPK signalling/ion channels/other components identified in the network underpin the effects of CaMKII protein knockdown on adult worm vitality.…”

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

“…For example, Smp_026510 (MEK2) is a putative target of CaMKII and this protein is an upstream regulator of ERK, a protein that we found to be phosphorylated by PZQ exposure and to profoundly affect S. mansoni motility, pairing, attachment, and egg release 38 . Moreover, the notch pathway has been found to regulate oogenesis and embryogenesis in S. mansoni 53 . Given that Wnt and notch are central to organism development, it is possible that CaMKII interactions with MAPK signalling/ion channels/other components identi ed in the network underpin the effects of CaMKII protein knockdown on adult worm vitality.…”

Main Pathways and Ion Channels Differentially Expressed in the Transcriptome of Male and Female Adult Angiostrongylus can-tonensis using a Deep Sequencing Approach

“…In C. elegans and Drosophila melanogaster , TGF-β-related proteins balance germ cell proliferation and differentiation ( 28 , 29 ). The Notch pathway in Schistosoma Mansoni is involved in parasite oogenesis and embryogenesis ( 30 ). As an evolutionarily conserved energy sensor, AMPK is involved in the regulation of energy metabolism in many organisms, including pigs ( Sus scrofa ), mice ( Mus musculus ), flies ( Drosophila melanogaster ), and worms ( Caenorhabditis elegans ) ( 31 , 32 ).…”