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

Authors: Durak, Omer; de Anda, Froylan Calderon; Singh, Karun K.; Leussis, Melanie P.; Sklar, Pamela; Tsai, Li-Huei; Petryshen, Tracey L.;

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

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.

Country
United States
Keywords

Ankyrins, Neurogenesis, 610, Neuropsychiatric Disorders, Mice, Transgenic, Ankyrin-G, ANK3, Article, Wnt, Mice, Pregnancy, Cell Line, Tumor, Animals, Wnt Signaling Pathway, Cells, Cultured, Cell Proliferation, Cerebral Cortex, Neurons, Carcinoma, Gene Expression Regulation, Developmental, Embryo, Mammalian, Actins, Wnt Proteins, Female, Subcellular Fractions

  • BIP!
    Impact byBIP!
    selected citations
    These citations are derived from selected sources.
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    61
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
61
Top 10%
Top 10%
Top 10%
Green
bronze