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Updated: Jun 2, 2026

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

Recombinant WNTs differentially activate β-catenin-dependent and -independent signalling in mouse microglia-like

M B C Kilander1, C Halleskog, G Schulte

  • 1Section Receptor Biology & Signalling, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

Acta Physiologica (Oxford, England)
|May 12, 2011
PubMed
Abstract

Insights

Different Wingless/Int-1 (WNTs) vary in activating WNT/β-catenin signaling and cell proliferation in microglia. WNT-3A activates β-catenin signaling, while WNT-5A and WNT-9B promote cell growth, highlighting WNTs

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Wingless/Int-1 (WNT) proteins are crucial signaling molecules involved in development and cell function.
  • Microglia, the immune cells of the central nervous system, play roles in neuroinflammation and neurodevelopment.
  • Understanding WNT signaling in microglia is essential for comprehending brain maturation and disease.

Purpose of the Study:

  • To compare the efficacy of various recombinant Wingless/Int-1 (WNTs) in activating key signaling pathways.
  • To investigate the impact of different WNTs on dishevelled (DVL) and G protein activation in microglia.
  • To assess the WNT-induced cell proliferation in a microglia-like cell line (N13).

Main Methods:

  • Immunoblotting was used to detect activated signaling molecules in cell lysates.
  • A [γ(35)S] GTP binding assay measured heterotrimeric G protein activation in N13 membrane preparations.
  • Cell proliferation was quantified using the MTT assay to measure mitochondrial activity.

Main Results:

  • Only WNT-3A effectively activated the WNT/β-catenin signaling pathway in N13 cells.
  • All tested WNTs induced dishevelled (DVL) phosphorylation and G protein activation, with varying efficacies.
  • WNT-5A and WNT-9B demonstrated the highest efficacy in G protein activation and significantly promoted N13 cell proliferation.

Conclusions:

  • Significant differences exist in the ability of WNTs to activate β-catenin-dependent and -independent signaling pathways.
  • The WNTs studied are present in the developing and adult brain, suggesting their role in regulating microglia.
  • These findings indicate that WNTs are potential regulators of microglia-mediated neuroinflammation.

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