Mest/Peg1 inhibits Wnt signalling through regulation of LRP6 glycosylation

Mest (mesoderm-specific transcript)/Peg 1 (paternally expressed gene 1) is an imprinted gene that plays important roles in embryo development, although its biochemical role has not been determined. Ectopic expression of Mest/Peg 1 inhibited Wnt-mediated reporter activity by enhancing the ubiquitination of beta-catenin. The maturation and plasma membrane localization of the Wnt co-receptor LRP6 [LDLR (low-density lipoprotein receptor)-related protein 6], which are both necessary for Wnt signalling, were blocked by the expression of Mest/Peg 1. Mest/Peg 1 inhibited maturation of LRP6 by controlling the glycosylation of LRP6. Knockdown of Mest/Peg 1, which might enhance Wnt signalling, blocked adipogenic differentiation of 3T3-L1 cells. Overall, our results suggest that Mest/Peg 1 is a novel regulator of Wnt/beta-catenin signalling during adipogenic differentiation.