The Wnt/planar cell polarity pathway component Vangl2 induces synapse formation through direct control of N-cadherin

Tadahiro Nagaoka, Riuko Ohashi, Ayumu Inutsuka, Seiko Sakai, Nobuyoshi Fujisawa, Minesuke Yokoyama, Yina H. Huang, Michihiro Igarashi, Masashi Kishi

研究成果: Article査読

46 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)916-927
ページ数12
ジャーナルCell Reports
6
5
DOI
出版ステータスPublished - 2014
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)

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