The Drosophila Activin-like ligand Dawdle signals preferentially through one isoform of the Type-I receptor Baboon

Abstract

How TGF-β-type ligands achieve signaling specificity during development is only partially understood. Here we show that Dawdle, one of four Activin-type ligands in Drosophila, preferentially signals through Baboc, one of three isoforms of the Activin Type-I receptor that are expressed during development. In cell culture, Dawdle signaling is active in the presence of the Type-II receptor Punt but not Wit, demonstrating that the Type-II receptor also contributes to the specificity of the signaling complex. During development, different larval tissues express unique combinations of these receptors, and ectopic expression of Baboc in a tissue were it is not normally expressed at high levels can make that tissue sensitive to Dawdle signaling. These results reveal a mechanism by which distinct cell types can discriminate between different Activin-type signals during development as a result of differential expression of Type-I receptor isoforms.

CTCF-dependent co-localization of canonical Smad signaling factors at architectural protein binding sites in D. melanogaster

“…44,45 TGF-b/Activin ligands signal through splice isoforms of the Baboon receptor to activate the R-Smad dSmad2 (Smad on X). [46][47][48] The phosphorylated forms of dSmad2 and Mad are able to form heterotrimeric complexes with the co-Smad Medea, and upon which translocate into the nucleus to direct changes in transcription. 49 The Mad/ Medea complex has been shown to target activation regulatory elements in response to DPP, 50 as well as repressive regulatory elements to which the transcriptional repressor Schnurri is recruited.…”

Appendage regeneration after autotomy is mediated by Baboon in the crayfish Procambarus fallax f. virginalis Martin, Dorn, Kawai, Heiden and Scholtz, 2010 (Decapoda: Astacoidea: Cambaridae)

“…Babo has been extensively studied in Drosophila, but less information is available in other arthropod species. Drosophila shows multiple transcriptional variants of babo, which differ only in the ex- tracellular domain that is critical for ligand binding (Wrana et al, 1994;Brummel et al, 1999;Jensen et al, 2009). Our results also suggest at least two functional splice variants of babo in this species that differ in the activin-receptor domain.…”

“…In this study, the complete exon-intron structures are not clear because no genomic information is available for this species. There is nevertheless only one exon resulting from the variation of the activin-receptor domain in Drosophila (Jensen et al, 2009); the insertion of the 65 bp predicted exon in babo C therefore implies that the construction of exons are different between decapod crustaceans and insects. Similar to Babo isoforms in Drosophila (Jensen et al, 2009), the differences of activin-receptor domains are expected to enable the isoforms to exhibit different ligand binding characteristics.…”

“…The functions of the two isoforms identified in this study are likely to be different because they vary in the receptor domain. The variation in the receptor domain indicates that the two isoforms have different ligands (Jensen et al, 2009). The candidate ligands include dActivin, Dawdle, Myoglianin, and Maverick (Parker et al, 2004).…”

Strategies for exploring TGF-β signaling in Drosophila

“…The Maverick ligand cannot be easily categorized based on sequence alignment [12], illustrating the trend that ligands tend to have greater sequence diversity than other players. Finally, the Baboon Type I receptor has three isoforms that differ only in the ligand binding domain [13–14] thereby potentially supplying signaling specificity for three different ligands; it is not clear how prevalent this strategy is in different animals. A suite of regulatory molecules that are often considered part of the network are also encoded in the fruit fly genome.…”