Disruption of protein O-glycosylation alters FGF signaling by modulating basement membrane composition

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NIDCR	DEV-10

Authors

• E Tian
• M Hoffman
• K Ten Hagen

Abstract

Cellular microenvironments are a complex array of components that influence cell signaling, proliferation and differentiation, but the diverse factors that regulate the composition of the extracellular matrix (ECM) are not completely understood. Recent studies have demonstrated that protein O-glycosylation can influence the composition of the ECM in Drosophila. Here we demonstrate that this conserved protein modification affects FGF-mediated cell proliferation during mammalian organogenesis by influencing ECM composition. Mice deficient for an enzyme (ppGalNAcT-1) that adds sugars to proteins during early development of submandibular glands resulted in intracellular accumulation of major basement membrane (BM) proteins, reduced FGF signaling, reduced AKT and MAPK phosphorylation and reduced epithelial cell proliferation. Exogenous addition of BM components to ppGalNAcT-1 deficient glands rescued FGF signaling and the growth defects observed. Our work demonstrates that O-glycosylation influences the composition of the ECM in mammalian organ development, with resultant effects on cell signaling, proliferation and organ growth.These results highlight a conserved role for O-glycosylation in the establishment of cellular microenvironments and have implications for the role of this protein modification in both development and disease.

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