O-glycosylation modulates integrin and FGFsignalling by influencing the secretion of basementmembrane components

摘要

Extracellular microenvironments have crucial roles in modulating cell interactions duringdevelopment. Here we discover that a conserved protein modification (o-glycosylation)influences extracellular matrix composition during mammalian organogenesis, affecting integrinsignalling and fibroblast growth factor-mediated cell proliferation. specifically, mice deficient foran enzyme (Galnt1) that adds sugars to proteins during early stages of organogenesis resulted inintracellular accumulation of major basement membrane proteins and endoplasmic reticulumstress, with resultant effects on fibroblast growth factor signalling, epithelial cell proliferationand organ growth. Exogenous addition of basement membrane components rescued fibroblastgrowth factor signalling and the growth defects in a beta 1-integrin-dependent manner. ourwork demonstrates for the first time that o-glycosylation influences the composition of theextracellular matrix during mammalian organ development, influencing specific aspects of theendoplasmic reticulum stress response, cell signalling, cell proliferation and organ growth. ourwork provides insight into the role of this conserved protein modification in both developmentand disease.