PUBLICATION

In Situ Fucosylation of the Wnt Co-receptor LRP6 Increases Its Endocytosis and Reduces Wnt/β-Catenin Signaling

Authors
Hong, S., Feng, L., Yang, Y., Jiang, H., Hou, X., Guo, P., Marlow, F.L., Stanley, P., Wu, P.
ID
ZDB-PUB-210702-16
Date
2020
Source
Cell chemical biology   27: 1140-1150.e4 (Journal)
Registered Authors
Marlow, Florence
Keywords
(1–3)-fucosylation, LRP6, Wnt signaling/β-catenin signaling, endocytosis
MeSH Terms
  • Animals
  • CHO Cells
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Embryo, Nonmammalian/metabolism
  • Endocytosis*/drug effects
  • Fucose/metabolism*
  • Fucose/pharmacology
  • Glycosylation
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-6/genetics
  • Low Density Lipoprotein Receptor-Related Protein-6/metabolism*
  • Membrane Microdomains/metabolism
  • Monosaccharide Transport Proteins/genetics
  • Monosaccharide Transport Proteins/metabolism
  • Wnt Proteins/antagonists & inhibitors
  • Wnt Proteins/metabolism
  • Wnt Signaling Pathway*
  • Zebrafish/growth & development
  • Zebrafish/metabolism
  • beta Catenin/metabolism
PubMed
32649905 Full text @ Cell Chem Biol
Abstract
Wnt/β-catenin signaling regulates critical, context-dependent transcription in numerous physiological events. Among the well-documented mechanisms affecting Wnt/β-catenin activity, modification of N-glycans by L-fucose is the newest and the least understood. Using a combination of Chinese hamster ovary cell mutants with different fucosylation levels and cell-surface fucose editing (in situ fucosylation [ISF]), we report that α(1-3)-fucosylation of N-acetylglucosamine (GlcNAc) in the Galβ(1-4)-GlcNAc sequences of complex N-glycans modulates Wnt/β-catenin activity by regulating the endocytosis of low-density lipoprotein receptor-related protein 6 (LRP6). Pulse-chase experiments reveal that ISF elevates endocytosis of lipid-raft-localized LRP6, leading to the suppression of Wnt/β-catenin signaling. Remarkably, Wnt activity decreased by ISF is fully reversed by the exogenously added fucose. The combined data show that in situ cell-surface fucosylation can be exploited to regulate a specific signaling pathway via endocytosis promoted by a fucose-binding protein, thereby linking glycosylation of a receptor with its intracellular signaling.
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