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

Senlian Hong, Lei Feng, Yi Yang, Hao Jiang, Xiaomeng Hou, Peng Guo, Florence L. Marlow, Pamela Stanley, Peng Wu

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1140-1150.e4
JournalCell Chemical Biology
Volume27
Issue number9
DOIs
StatePublished - Sep 17 2020

Keywords

  • (1–3)-fucosylation
  • LRP6
  • Wnt signaling/β-catenin signaling
  • endocytosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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