Structural and functional evidences for a type 1 TGF-beta sensu stricto receptor in the lophotrochozoan Crassostrea...

The transforming growth factor beta (TGFbeta) superfamily includes bone morphogenetic proteins, activins and TGF-betasensu stricto (s.s.). These ligands have been shown to play a key role in numerous biological processes including early embryonic development and immune regulation. They transduce their signal through a hetromeric complex of type I and type II receptors. Such receptors have been identified in ecdysozoans but none have been found as yet in the other major protostomal clade, the lophotrochozoans. Here, we report the identification of the first lophotrochozoan TGFbetas.s. type I receptor (Cg-TGFbetaRI) from the mollusk Crassostrea gigas. The phylogenetic and structural analyses as well as the expression pattern during early development suggest Cg-TGFbetaRI to belong to the TGFbetas.s./activin type I receptor clade and functional studies corroborate these deductions. The use of the zebrafish embryo as a reporter organism reveals that either Cg-TGFbetaRI or its dominant negative acting truncated form, when overexpressed during gastrulation, resulted in a range of phenotypes displaying severe disturbance of anterioposterior patterning due to a strong modulation of ventrolateral mesoderm patterning. Finally, a Cg-TGFbetaRI cytokine activity during immune regulation in C. gigas has been investigated by real-time PCR in haemocytes and mantle edge during an in vivo bacterial LPS challenge. One piece of evidence from this study suggests that the molecular mechanisms controlling mesodermal patterning and some immune regulations across all bilateria could be conserved through a functional TGF-beta s.s. pathway in lophotrochozoans.