Ankyrin-G regulates neurogenesis and Wnt signaling by altering the subcellular localization of β-catenin
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Ankyrin-G regulates neurogenesis and Wnt signaling by altering the subcellular localization of β-catenin. / Durak, Omer; Calderon de Anda, Froylan; Singh, Karun K. ; Leussis, Melanie P.; Petryshen, Tracey L; Sklar, Pamela; Tsai, Li-Huei.
In: MOL PSYCHIATR, Vol. 20, No. 3, 03.2015, p. 388-397.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Ankyrin-G regulates neurogenesis and Wnt signaling by altering the subcellular localization of β-catenin
AU - Durak, Omer
AU - Calderon de Anda, Froylan
AU - Singh, Karun K.
AU - Leussis, Melanie P.
AU - Petryshen, Tracey L
AU - Sklar, Pamela
AU - Tsai, Li-Huei
PY - 2015/3
Y1 - 2015/3
N2 - 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 (BD), schizophrenia, and autism spectrum disorder (ASD). 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. Together, these results suggest that ankyrin-G is required for proper brain development.
AB - 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 (BD), schizophrenia, and autism spectrum disorder (ASD). 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. Together, these results suggest that ankyrin-G is required for proper brain development.
M3 - SCORING: Journal article
VL - 20
SP - 388
EP - 397
JO - MOL PSYCHIATR
JF - MOL PSYCHIATR
SN - 1359-4184
IS - 3
ER -
