Functional conservation of Schistosoma mansoni Smads in TGF-beta signaling

To begin to understand the molecular basis of communication between the parasite Schistosoma mansoni and its mammalian host, we are studying the signaling pathway downstream of S. mansoni receptor kinase-1 (SmRK1), a divergent type I transforming growth factor-beta (TGF-beta) receptor found on the tegumental surface of the parasite. In this study, we have used a homology based PCR approach to clone two S. mansoni Smad (SmSmad) genes; Smads play a pivotal role in the most well understood signaling pathways initiated by the TGF-beta family of ligands in other organisms. Comparison of the amino acid sequences with those of other Smads reveals that the conserved MH1 and MH2 domains of SmSmads show a high degree of identity to homologues in Drosophila. Transcripts for both SmSmads are detected in the same developmental stages as SmRK1, and both are capable of interacting with the intracellular domain of the receptor in vitro. Functional characterization using the human type I TGF-beta receptor further confirms the highly conserved nature of these proteins, as both SmSmads show TGF-beta dependent enhancement of luciferase activity and nuclear translocation in mammalian cells. These data are the first to show a TGF-beta-like receptor/Smad signaling pathway in parasitic helminths and by analogy with other systems, is likely important in regulating schistosome development.