Open AccessN-linked glycosylation restricts the function of short gastrulation to bind and shuttle BMPs
Author(s) -
Érika Negreiros,
Sophie Herszterg,
KyungHwa Kang,
Amanda R. Câmara,
Wagner B. Dias,
Kátia Carneiro,
Ethan Bier,
Adriane R. Todeschini,
Helena Araujo
Publication year - 2018
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.167338
Subject(s) - biology , chordin , glycosylation , gastrulation , bone morphogenetic protein , microbiology and biotechnology , extracellular , function (biology) , conserved sequence , genetics , peptide sequence , embryo , gene , embryogenesis
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 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.