title: Adaptive protein divergence of BMP ligands takes place under developmental and evolutionary constraints.
abstract: The bone morphogenetic protein (BMP) signaling network, comprising evolutionary conserved BMP2/4/Decapentaplegic (Dpp) and Chordin/Short gastrulation (Sog), is widely utilized for dorsal-ventral (DV) patterning during animal development. A similar network is required for posterior crossvein (PCV) formation in the Drosophila pupal wing. Although both transcriptional and post-transcriptional regulation of co-factors in the network gives rise to tissue-specific and species-specific properties, their mechanisms are incompletely understood. In Drosophila, BMP5/6/7/8-type ligands, Screw (Scw) and Glass bottom boat (Gbb), form heterodimers with Dpp for DV patterning and PCV development, respectively. Sequence analysis indicates that the Scw ligand contains two N-glycosylation motifs: one being highly conserved between BMP2/4- and BMP5/6/7/8-type ligands, and the other being Scw ligand specific. Our data reveal that N-glycosylation of the Scw ligand boosts BMP signaling both in cell culture and in the embryo. In contrast, N-glycosylation modifications of Gbb or Scw ligands reduce the consistency of PCV development. These results suggest that tolerance for structural changes of BMP5/6/7/8-type ligands is dependent on developmental constraints. Furthermore, gain and loss of N-glycosylation motifs in conserved signaling molecules under evolutionary constraints appear to constitute flexible modules to adapt to developmental processes.
authors: Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland.
authors: Petra M
authors: PM
authors: Tauscher
authors: Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland.
authors: Jinghua
authors: J
authors: Gui
authors: Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland osamu.shimmi@helsinki.fi.
authors: Osamu
authors: 0000-0001-6341-9130
authors: O
authors: Shimmi
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D006031:Glycosylation; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014921:Wings, Animal / Q000196:embryology / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins
keywords: Bone morphogenetic protein (BMP); Drosophila; N-glycosylation; Patterning; Post-transcriptional regulation; Protein evolution