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.
| 元の言語 | English |
|---|---|
| ページ（範囲） | 916-927 |
| ページ数 | 12 |
| ジャーナル | Cell Reports |
| 巻 | 6 |
| 発行部数 | 5 |
| DOI | |
| 出版物ステータス | Published - 01-01-2014 |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
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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.
：: Cell Reports, 巻 6, 番号 5, 01.01.2014, p. 916-927.研究成果: Article
TY - JOUR
T1 - The Wnt/planar cell polarity pathway component Vangl2 induces synapse formation through direct control of N-cadherin
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
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84895923250&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2014.01.044
DO - 10.1016/j.celrep.2014.01.044
M3 - Article
C2 - 24582966
AN - SCOPUS:84895923250
VL - 6
SP - 916
EP - 927
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 5
ER -