Ankyrin-G regulates neurogenesis and Wnt signaling by altering the subcellular localization of β-catenin.
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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
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Journal | Mol Psychiatry
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Volume | 20
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Issue | 3
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Pages | 388-97
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Date Published | 2015 Mar
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ISSN | 1476-5578
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DOI | 10.1038/mp.2014.42
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PubMed ID | 24821222
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PubMed Central ID | PMC4231016
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Grant list | R01 MH091115 / MH / NIMH NIH HHS / United States
MH091115 / MH / NIMH NIH HHS / United States
Howard Hughes Medical Institute / United States
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