Ankyrin-G regulates neurogenesis and Wnt signaling by altering the subcellular localization of β-catenin
Name
Tsai_Ankyrin-G regulates.pdf
Size
2.67 MB
Format
Adobe PDF
Checksum (MD5)
0f552a4a8d619f1efd7c932d69ecbe3d
Author(s)
Durak, Omer
Calderon de Anda, Froylan
Singh, Karuna K.
Leussis, M. P.
Petryshen, T. L.
Sklar, P.
Tsai, Li-Huei
Date Issued
May 2014
Journal
Molecular Psychiatry
Publisher
Nature Publishing Group
Citation
Durak, O, F C de Anda, K K Singh, M P Leussis, T L Petryshen, P Sklar, and L-H Tsai. “Ankyrin-G Regulates Neurogenesis and Wnt Signaling by Altering the Subcellular Localization of β-Catenin.” Mol Psychiatry 20, no. 3 (May 13, 2014): 388–397.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/mp.2014.42
