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Mol 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 Publication2015
AuthorsDurak, O, de Anda, FC, Singh, KK, Leussis, MP, Petryshen, TL, Sklar, P, Tsai, L-H
JournalMol Psychiatry
Date Published2015 Mar
KeywordsActins, Animals, Ankyrins, Carcinoma, Cell Line, Tumor, Cell Proliferation, Cells, Cultured, Cerebral Cortex, Embryo, Mammalian, Female, Gene Expression Regulation, Developmental, Mice, Mice, Transgenic, Neurogenesis, Neurons, Pregnancy, Subcellular Fractions, Wnt Proteins, Wnt Signaling Pathway

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.


Alternate JournalMol. Psychiatry
PubMed ID24821222
PubMed Central IDPMC4231016
Grant ListR01 MH091115 / MH / NIMH NIH HHS / United States
MH091115 / MH / NIMH NIH HHS / United States
/ / Howard Hughes Medical Institute / United States