O-glycosylation modulates integrin and FGF signaling by influencing the secretion of basement membrane components

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NIDCR	DEV-15

Authors

• E Tian
• M.P. Hoffman
• K.G. Ten Hagen

Abstract

Extracellular microenvironments play crucial roles in modulating cell interactions during development. Here we discover that a conserved protein modification (O-glycosylation) influences extracellular matrix (ECM) composition during mammalian organogenesis, affecting integrin signaling and FGF-mediated cell proliferation. Specifically, mice deficient for an enzyme (Galnt1) that adds sugars to proteins during early stages of organogenesis resulted in intracellular accumulation of major basement membrane (BM) proteins and ER stress, with resultant effects on FGF signaling, epithelial cell proliferation and organ growth. Exogenous addition of BM components rescued FGF signaling and the growth defects in a β1-integrin-dependent manner. Our work demonstrates for the first time that O-glycosylation influences the composition of the ECM during mammalian organ development, influencing specific aspects of the ER stress response, cell signaling, cell proliferation and organ growth. Our work provides insight into the role of this conserved protein modification in both development and disease.

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