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FEBS J. 2017 Aug;284(15):2513-2526. doi: 10.1111/febs.14139. Epub 2017 Jul 6.

Binding of canonical Wnt ligands to their receptor complexes occurs in ordered plasma membrane environments.

Author information

1
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, UK.
2
Izmir International Biomedicine and Genome Institute (iBG-izmir), Dokuz Eylul University, Izmir, Turkey.
3
Department of Medical Biology and Genetics, Dokuz Eylul University Medical School, Izmir, Turkey.
4
Department of Chemistry and Center for BioImaging Sciences, National University of Singapore, Singapore.
5
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore.
6
Max Planck Institute of Cell Biology and Genetics, Dresden, Germany.
7
Institute of Biochemistry and Molecular Biology, Ulm University, Germany.

Abstract

While the cytosolic events of Wnt/β-catenin signaling (canonical Wnt signaling) pathway have been widely studied, only little is known about the molecular mechanisms involved in Wnt binding to its receptors at the plasma membrane. Here, we reveal the influence of the immediate plasma membrane environment on the canonical Wnt-receptor interaction. While the receptors are distributed both in ordered and disordered environments, Wnt binding to its receptors selectively occurs in more ordered membrane environments which appear to cointernalize with the Wnt-receptor complex. Moreover, Wnt/β-catenin signaling is significantly reduced when the membrane order is disturbed by specific inhibitors of certain lipids that prefer to localize at the ordered environments. Similarly, a reduction in Wnt signaling activity is observed in Niemann-Pick Type C disease cells where trafficking of ordered membrane lipid components to the plasma membrane is genetically impaired. We thus conclude that ordered plasma membrane environments are essential for binding of canonical Wnts to their receptor complexes and downstream signaling activity.

KEYWORDS:

Wnt/β-catenin pathway; canonical Wnt; lipid raft; membrane trafficking; plasma membrane lipid

PMID:
28626941
PMCID:
PMC5599997
DOI:
10.1111/febs.14139
[Indexed for MEDLINE]
Free PMC Article

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