title: 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.
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: O
authors.initials: O
authors.lastname: Durak
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: F C
authors.initials: FC
authors.lastname: de Anda
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Singh
authors.affiliation: 1] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA [2] Department of Psychiatry, Harvard Medical School, Boston, MA, USA [3] Stanley Center for Psychiatric Research, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Leussis
authors.affiliation: 1] Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA [2] Department of Psychiatry, Harvard Medical School, Boston, MA, USA [3] Stanley Center for Psychiatric Research, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Petryshen
authors.affiliation: Division of Psychiatric Genomics, Departments of Psychiatry, Neuroscience and Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: P
authors.initials: P
authors.lastname: Sklar
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: L-H
authors.initials: LH
authors.lastname: Tsai
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017487:Ankyrins / Q000172:deficiency; D002277:Carcinoma / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy; D013347:Subcellular Fractions / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics*
chemical_list: D000199:Actins; C094681:Ank3 protein, mouse; D017487:Ankyrins; D051153:Wnt Proteins