The Wnt/Planar Cell Polarity Pathway Component Vangl2 Induces Synapse Formation through Direct Control of N-Cadherin

• DOI: 10.1016/j.celrep.2014.01.044
• Publication Date: 2014-02-27T17:15:20Z
• Authors: Tadahiro Nagaoka; Riuko Ohashi; Ayumu Inutsuka; Seiko Sakai; Nobuyoshi Fujisawa; Minesuke Yokoyama; Yina H. Huang; Michihiro Igarashi; Masashi Kishi
• Keywords: Male; 0303 health sciences; QH301-705.5; Intracellular Signaling Peptides and Proteins; Cell Polarity; Membrane Proteins; Cadherins; Transfection; Madin Darby Canine Kidney Cells; Rats; Mice, Inbred C57BL; Wnt Proteins; Mice; 03 medical and health sciences; Dogs; HEK293 Cells; COS Cells; Chlorocebus aethiops; Synapses; Animals; Humans; Drosophila; Biology (General)

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.