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

Publication TypeJournal Article
AuthorsDurak, O., de Anda FC, Singh KK, Leussis MP, Petryshen TL, Sklar P., and Tsai LH
AbstractAnkyrin-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.Molecular Psychiatry advance online publication, 13 May 2014; doi:10.1038/mp.2014.42.
Year of Publication2014
JournalMolecular psychiatry
Date Published (YYYY/MM/DD)2014/05/13
ISSN Number1359-4184
DOI10.1038/mp.2014.42
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/24821222?dopt=Abstract