N-linked glycosylation of the antagonist Short gastrulation increases the functional complexity of BMP signals [article]

Erika Negreiros, Sophie Herszterg, Kyung-Hwa Kang, Amanda Camara, Wagner Dias, Katia Carneiro, Ethan Bier, Adriane Todeschini, Helena Araujo
2018 bioRxiv   pre-print
Disorders of N-linked glycosylation are increasingly reported in the literature. However, targets responsible for the associated developmental and physiological defects are largely unknown. Bone Morphogenetic Proteins (BMPs) act as highly dynamic complexes to regulate several functions during development. The range and strength of BMP activity depend on interactions with glycosylated protein complexes in the extracellular milieu. Here we investigate the role of glycosylation for the function of
more » ... the conserved extracellular BMP antagonist Short gastrulation (Sog). We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila. Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue. Mechanistically, we provide evidence that N-terminal and stem glycosylation controls extracellular Sog levels and distribution. The identification of similar residues in vertebrate Chordin proteins suggests that N-glycosylation may be an evolutionarily conserved process that adds complexity to the regulation of BMP activity.
doi:10.1101/316448 fatcat:oxqc34z3pzaxxg344rf3iu7crm