Xu X, Li W E, Huang G Y, Meyer R, Chen T, Luo Y, Thomas M P, Radice G L, Lo C W
Biology Department, Goddard Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Cell Biol. 2001 Jul 9;154(1):217-30. doi: 10.1083/jcb.200105047.
Connexin 43 (Cx43alpha1) gap junction has been shown to have an essential role in mediating functional coupling of neural crest cells and in modulating neural crest cell migration. Here, we showed that N-cadherin and wnt1 are required for efficient dye coupling but not for the expression of Cx43alpha1 gap junctions in neural crest cells. Cell motility was found to be altered in the N-cadherin-deficient neural crest cells, but the alterations were different from that elicited by Cx43alpha1 deficiency. In contrast, wnt1-deficient neural crest cells showed no discernible change in cell motility. These observations suggest that dye coupling may not be a good measure of gap junction communication relevant to motility. Alternatively, Cx43alpha1 may serve a novel function in motility. We observed that p120 catenin (p120ctn), an Armadillo protein known to modulate cell motility, is colocalized not only with N-cadherin but also with Cx43alpha1. Moreover, the subcellular distribution of p120ctn was altered with N-cadherin or Cx43alpha1 deficiency. Based on these findings, we propose a model in which Cx43alpha1 and N-cadherin may modulate neural crest cell motility by engaging in a dynamic cross-talk with the cell's locomotory apparatus through p120ctn signaling.
连接蛋白43（Cx43α1）间隙连接已被证明在介导神经嵴细胞的功能偶联以及调节神经嵴细胞迁移中起重要作用。在此，我们表明N-钙黏蛋白和Wnt1对于神经嵴细胞中高效的染料偶联是必需的，但对于Cx43α1间隙连接的表达并非必需。我们发现N-钙黏蛋白缺陷的神经嵴细胞的细胞运动性发生了改变，但这些改变与Cx43α1缺陷引起的改变不同。相比之下，Wnt1缺陷的神经嵴细胞在细胞运动性方面没有明显变化。这些观察结果表明，染料偶联可能不是衡量与运动性相关的间隙连接通讯的良好指标。或者，Cx43α1可能在运动性中发挥新的功能。我们观察到，已知可调节细胞运动性的犰狳蛋白p120连环蛋白（p120ctn）不仅与N-钙黏蛋白共定位，还与Cx43α1共定位。此外，p120ctn的亚细胞分布随N-钙黏蛋白或Cx43α1缺陷而改变。基于这些发现，我们提出一个模型，其中Cx43α1和N-钙黏蛋白可能通过p120ctn信号传导与细胞的运动装置进行动态相互作用来调节神经嵴细胞的运动性。
