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Amer2 protein is a novel negative regulator of Wnt/β-catenin signaling involved in neuroectodermal patterning

Astrid S Pfister1, Kristina Tanneberger, Alexandra Schambony

  • 1Nikolaus Fiebiger Center for Molecular Medicine, University Erlangen-Nuremberg, 91054 Erlangen, Germany.

The Journal of Biological Chemistry
|December 1, 2011
PubMed

Insights

Amer2 protein recruits adenomatous polyposis coli (APC) to cell membranes, negatively regulating Wnt/β-catenin signaling. This discovery identifies Amer proteins as novel Wnt pathway regulators in both cell lines and developing embryos.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Developmental Biology

Background:

  • Wnt/β-catenin signaling is crucial for development and disease.
  • Adenomatous polyposis coli (APC) is a key negative regulator of this pathway.
  • The function of Amer2 (APC membrane recruitment 2; FAM123A) in Wnt signaling was previously unknown.

Purpose of the Study:

  • To investigate the role of Amer2 in Wnt/β-catenin signaling.
  • To elucidate the mechanism by which Amer2 regulates APC.
  • To determine the in vivo function of Amer2 in embryonic development.

Main Methods:

  • Co-immunoprecipitation assays to identify protein interactions.
  • Cell-based assays measuring Wnt target gene expression and reporter activity.
  • Analysis of Amer2 localization and function in Xenopus embryos using morpholino knockdown and rescue experiments.

Main Results:

  • Amer2 directly binds to APC and recruits it to the plasma membrane via phosphatidylinositol 4,5-bisphosphate lipids.
  • Knockdown of Amer2 enhances Wnt signaling, while overexpression inhibits it, dependent on membrane localization.
  • Amer2 regulates neuroectodermal patterning in Xenopus embryos, and its absence leads to altered Wnt signaling.

Conclusions:

  • Amer2 functions as a novel negative regulator of Wnt/β-catenin signaling.
  • Amer2's recruitment of APC to the membrane is critical for its inhibitory function.
  • Amer proteins represent a new family of regulators for the Wnt pathway, with implications for development and disease.

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