Cadherin-11 interacts with the FGF receptor and induces neurite outgrowth through associated downstream signalling
Cadherin-11 interacts with the FGF receptor and induces neurite outgrowth through associated downstream signalling
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DOI：
10.1016/j.cellsig.2008.01.008
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发表时间：
2008-06-01
影响因子：
4.8
通讯作者：
Mege, Rene-Marc
中科院分区：
文献类型：
--
作者：
Boscher, Cecile;Mege, Rene-Marc
钙粘蛋白-11是一种细胞-细胞粘附分子，其表达通常与细胞迁移现象相关。我们最近证明，钙粘蛋白-11激活固定cad 11-Fc（钙粘蛋白-11胞外域融合到Fc片段）促进脊髓外植体的轴突延伸。在这里，我们表明，这种诱导的轴突生长是依赖于FGF受体（FGFR）的活动。下游需要DAG脂肪酶/CAM激酶和PI 3激酶途径，但不需要MAP激酶信号传导。我们还证明了FGFR 1的标记形式与含有钙粘蛋白-11免疫复合物的β-连环蛋白共免疫沉淀。FGFR 1和β-连环蛋白在钙粘蛋白-11接合期间显示共定位和增强的关联，表明FGFR 1与钙粘蛋白-11粘附复合物的相互作用在细胞接触形成期间得到加强。使用重组胞外域的体外下拉实验表明，钙粘蛋白-11/FGFR直接通过其胞外域相互作用。总之，我们认为钙粘蛋白-11在新生接触处的粘附接合后招募FGFR，触发参与生长锥进展的下游途径的激活。(C)2008年爱思唯尔公司All rights reserved.
Cadherin-11 is a cell-cell adhesion molecule whose expression is often correlated with cellular migratory phenomena. We recently demonstrated that cadherin-11 activation by immobilized cad11-Fc(cadherin-11 ectodomain fused to Fc fragment) promotes axonal extension of spinal cord explants. Here, we show that this induced neurite outgrowth is dependent on the FGF receptor (FGFR) activity. Downstream, DAG lipase/CAM kinase and PI3 kinase pathways are required, but not the MAP kinase signalling. We also demonstrate that a tagged form of FGFR1 co-immunoprecipitates with beta-catenin containing cadherin-11 immunocomplexes. FGFR1 and beta-catenin show colocalization and enhanced association during cadherin-11 engagement, suggesting that FGFR1 interaction with cadherin-11 adhesion complexes is reinforced during cell contact formation. In vitro pull-down experiments using recombinant ectodomains suggest that cadherin-11/FGFR interact directly through their extracellular domains. Altogether, we propose that cadherin-11 recruits the FGFR upon adhesive engagement at nascent contacts, triggering the activation of downstream pathways involved in growth cone progression. (C) 2008 Elsevier Inc. All rights reserved.