Ankyrin-G regulates neurogenesis and Wnt signaling by altering the subcellular localization of β-catenin
Author(s)Durak, Omer; Calderon de Anda, Froylan; Singh, Karuna K.; Leussis, M. P.; Petryshen, T. L.; Sklar, P.; Tsai, Li-Huei; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Picower Institute for Learning and Memory
Nature Publishing Group
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.
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