Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Durak, O, de Anda, FC, Singh, KK, Leussis, MP, Petryshen, TL, Sklar, P, Tsai, L-H |
Journal | Mol Psychiatry |
Volume | 20 |
Issue | 3 |
Pages | 388-97 |
Date Published | 2015 Mar |
ISSN | 1476-5578 |
Keywords | Actins, 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 |
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. |
URL | http://dx.doi.org/10.1038/mp.2014.42 |
DOI | 10.1038/mp.2014.42 |
Pubmed | |
Alternate Journal | Mol. Psychiatry |
PubMed ID | 24821222 |
PubMed Central ID | PMC4231016 |
Grant List | R01 MH091115 / MH / NIMH NIH HHS / United States MH091115 / MH / NIMH NIH HHS / United States / / Howard Hughes Medical Institute / United States |
Mol Psychiatry DOI:10.1038/mp.2014.42
Ankyrin-G regulates neurogenesis and Wnt signaling by altering the subcellular localization of β-catenin.
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