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

Research output: Contribution to journalArticle

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)916-927
Number of pages12
JournalCell Reports
Volume6
Issue number5
DOIs
Publication statusPublished - 01-01-2014

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Cell Polarity
Cadherins
Synapses
Catenins
Dendritic Spines
Cell adhesion
Neurology
Cellular Structures
Cell Adhesion
Nervous System
Neurons
Cluster Analysis
Vertebrates
Brain
Spine

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Nagaoka, Tadahiro ; Ohashi, Riuko ; Inutsuka, Ayumu ; Sakai, Seiko ; Fujisawa, Nobuyoshi ; Yokoyama, Minesuke ; Huang, Yina H. ; Igarashi, Michihiro ; Kishi, Masashi. / The Wnt/planar cell polarity pathway component Vangl2 induces synapse formation through direct control of N-cadherin. In: Cell Reports. 2014 ; Vol. 6, No. 5. pp. 916-927.
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Nagaoka, T, Ohashi, R, Inutsuka, A, Sakai, S, Fujisawa, N, Yokoyama, M, Huang, YH, Igarashi, M & Kishi, M 2014, 'The Wnt/planar cell polarity pathway component Vangl2 induces synapse formation through direct control of N-cadherin', Cell Reports, vol. 6, no. 5, pp. 916-927. https://doi.org/10.1016/j.celrep.2014.01.044

The Wnt/planar cell polarity pathway component Vangl2 induces synapse formation through direct control of N-cadherin. / Nagaoka, Tadahiro; Ohashi, Riuko; Inutsuka, Ayumu; Sakai, Seiko; Fujisawa, Nobuyoshi; Yokoyama, Minesuke; Huang, Yina H.; Igarashi, Michihiro; Kishi, Masashi.

In: Cell Reports, Vol. 6, No. 5, 01.01.2014, p. 916-927.

Research output: Contribution to journalArticle

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AU - Nagaoka, Tadahiro

AU - Ohashi, Riuko

AU - Inutsuka, Ayumu

AU - Sakai, Seiko

AU - Fujisawa, Nobuyoshi

AU - Yokoyama, Minesuke

AU - Huang, Yina H.

AU - Igarashi, Michihiro

AU - Kishi, Masashi

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