Cadherin-6B stimulates an epithelial mesenchymal transition and the delamination of cells from the neural ectoderm via LIMK/cofilin mediated non-canonical BMP receptor signaling.
Cadherin-6B stimulates an epithelial mesenchymal transition and the delamination of cells from the neural ectoderm via LIMK/cofilin mediated non-canonical BMP receptor signaling.
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DOI：
10.1016/j.ydbio.2012.04.005
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发表时间：
2012-06-15
影响因子：
2.7
通讯作者：
Gumbiner BM
中科院分区：
文献类型：
--
作者：
Park KS;Gumbiner BM
我们以前提供的证据表明，钙粘蛋白-6B诱导脱上皮神经嵴脱层之前，是所需的整体上皮间质转化（EMT）。此外，发现钙粘蛋白-6B诱导的去上皮化是由BMP受体信号传导介导的，不依赖于BMP。我们现在发现去上皮化是由通过BMP II型受体（BMPRII）的非规范BMP信号传导介导的，而不是由通过BMP I型受体的规范Smad依赖性信号传导介导的。LIM激酶/cofilin途径介导非经典BMPRII诱导的去上皮化，响应于钙粘蛋白-6B或BMP。LIMK 1诱导神经管中的去上皮化，并且显性阴性LIMK 1减少由钙粘蛋白-6B或BMP诱导的去上皮化。Cofilin是已知的主要LIMK 1靶标，并且S3 A磷酸化缺陷突变的Cofilin抑制由钙粘蛋白-6B以及LIMK 1诱导的去上皮化。重要的是，LIMK 1以及钙粘蛋白-6B可以触发异位分层时，与感受态因子SOX 9共表达，表明这种钙粘蛋白-6B刺激的信号通路可以介导在适当的情况下，完整的EMT。这些发现表明，神经嵴EMT的钙粘蛋白-6B/BMPRII的去上皮化步骤涉及通过LIMK/cofilin的肌动蛋白动力学的调节。
We previously provided evidence that cadherin-6B induces de-epithelialization of the neural crest prior to delamination and is required for the overall epithelial mesenchymal transition (EMT). Furthermore, de-epithelialization induced by cadherin-6B was found to be mediated by BMP receptor signaling independent of BMP. We now find that de-epithelialization is mediated by non-canonical BMP signaling through the BMP type II receptor (BMPRII) and not by canonical Smad dependent signaling through BMP Type I receptor. The LIM kinase/cofilin pathway mediates non-canonical BMPRII induced de-epithelialization, in response to either cadherin-6B or BMP. LIMK1 induces de-epithelialization in the neural tube and dominant negative LIMK1 decreases de-epithelialization induced by either cadherin-6B or BMP. Cofilin is the major known LIMK1 target and a S3A phosphorylation deficient mutated cofilin inhibits de-epithelialization induced by cadherin-6B as well as LIMK1. Importantly, LIMK1 as well as cadherin-6B can trigger ectopic delamination when co-expressed with the competence factor SOX9, showing that this cadherin-6B stimulated signaling pathway can mediate the full EMT in the appropriate context. These findings suggest that the de-epithelialization step of the neural crest EMT by cadherin-6B/BMPRII involves regulation of actin dynamics via LIMK/cofilin.
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影响因子：
9.2
作者：
Bravo-Cordero, Jose Javier;Oser, Matthew;Chen, Xiaoming;Eddy, Robert;Hodgson, Louis;Condeelis, John
通讯作者：
Condeelis, John
影响因子：
11.4
作者：
Lee-Hoeflich, ST;Causing, CG;Attisano, L
通讯作者：
Attisano, L
影响因子：
3.7
作者：
Foletta, VC;Moussi, N;Bernard, O
通讯作者：
Bernard, O
影响因子：
3.3
作者：
Nishihara, A;Watabe, T;Miyazono, K
通讯作者：
Miyazono, K
影响因子：
5.3
作者：
Chan, Mun Chun;Nguyen, Peter H.;Hata, Akiko
通讯作者：
Hata, Akiko