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Molecular psychiatry DOI:10.1038/mp.2014.42

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

Publication TypeJournal Article
Year of Publication2014
AuthorsDurak, O, de Anda, FC, Singh, KK, Leussis, MP, Petryshen, TL, Sklar, P, Tsai, LH
JournalMolecular psychiatry
Date Published2014/05/13

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.Molecular Psychiatry advance online publication, 13 May 2014; doi:10.1038/mp.2014.42.