Ankyrin-G regulates neurogenesis and Wnt signaling by altering the subcellular localization of β-catenin.

Mol Psychiatry
Authors
Keywords
Abstract

Ankyrin-G is a scaffolding protein required for the formation of the axon initial segment in neurons. Recent genome-wide association studies and whole-exome sequencing have identified ANK3, the gene coding for ankyrin-G, to be a risk gene for multiple neuropsychiatric disorders, such as bipolar disorder, schizophrenia and autism spectrum disorder. Here, we describe a novel role for ankyrin-G in neural progenitor proliferation in the developing cortex. We found that ankyrin-G regulates canonical Wnt signaling by altering the subcellular localization and availability of β-catenin in proliferating cells. Ankyrin-G loss-of-function increases β-catenin levels in the nucleus, thereby promoting neural progenitor proliferation. Importantly, abnormalities in proliferation can be rescued by reducing Wnt pathway signaling. Taken together, these results suggest that ankyrin-G is required for proper brain development.

Year of Publication
2015
Journal
Mol Psychiatry
Volume
20
Issue
3
Pages
388-97
Date Published
2015 Mar
ISSN
1476-5578
URL
DOI
10.1038/mp.2014.42
PubMed ID
24821222
PubMed Central ID
PMC4231016
Links
Grant list
R01 MH091115 / MH / NIMH NIH HHS / United States
MH091115 / MH / NIMH NIH HHS / United States
Howard Hughes Medical Institute / United States