title: The Wnt/planar cell polarity pathway component Vangl2 induces synapse formation through direct control of N-cadherin.
abstract: Although regulators of the Wnt/planar cell polarity (PCP) pathway are widely expressed in vertebrate nervous systems, their roles at synapses are unknown. Here, we show that Vangl2 is a postsynaptic factor crucial for synaptogenesis and that it coprecipitates with N-cadherin and PSD-95 from synapse-rich brain extracts. Vangl2 directly binds N-cadherin and enhances its internalization in a Rab5-dependent manner. This physical and functional interaction is suppressed by β-catenin, which binds the same intracellular region of N-cadherin as Vangl2. In hippocampal neurons expressing reduced Vangl2 levels, dendritic spine formation as well as synaptic marker clustering is significantly impaired. Furthermore, Prickle2, another postsynaptic PCP component, inhibits the N-cadherin-Vangl2 interaction and is required for normal spine formation. These results demonstrate direct control of classic cadherin by PCP factors; this control may play a central role in the precise formation and maturation of cell-cell adhesions at the synapse.
authors.affiliation: Laboratory of Molecular Neuroimaging, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Nagaoka
authors.affiliation: Division of Cellular and Molecular Pathology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.
authors.forename: Riuko
authors.initials: R
authors.lastname: Ohashi
authors.affiliation: Laboratory of Molecular Neuroimaging, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Inutsuka
authors.affiliation: Department of Comparative and Experimental Medicine, Brain Research Institute, Niigata University, Niigata 951-8510, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Department of Comparative and Experimental Medicine, Brain Research Institute, Niigata University, Niigata 951-8510, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Fujisawa
authors.affiliation: Department of Comparative and Experimental Medicine, Brain Research Institute, Niigata University, Niigata 951-8510, Japan.
authors.forename: Minesuke
authors.initials: M
authors.lastname: Yokoyama
authors.affiliation: Departments of Pathology and Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, NH 03755-1404, USA.
authors.forename: Yina H
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Neurochemistry and Molecular Cell Biology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Igarashi
authors.affiliation: Laboratory of Molecular Neuroimaging, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan. Electronic address: masashi.kishi@gmail.com.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kishi
mesh_terms: D000818:Animals; D019556:COS Cells; D015820:Cadherins / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D002522:Chlorocebus aethiops; D004285:Dogs; D004330:Drosophila; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D013569:Synapses / Q000378:metabolism*; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D015820:Cadherins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C468513:VANGL2 protein, human; D051153:Wnt Proteins