Assembly of connexin43 into gap junctions is regulated differentially by E-cadherin and N-cadherin in rat liver epithelial cells.
Assembly of connexin43 into gap junctions is regulated differentially by E-cadherin and N-cadherin in rat liver epithelial cells.
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DOI：
10.1091/mbc.e10-05-0403
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发表时间：
2010-12
影响因子：
3.3
通讯作者：
Mehta PP
中科院分区：
文献类型：
--
作者：
Govindarajan R;Chakraborty S;Johnson KE;Falk MM;Wheelock MJ;Johnson KR;Mehta PP
E-cadherin和N-cadherin对连接蛋白43组装成缝隙连接的影响不同。N-钙粘蛋白通过触发连接蛋白43的内吞作用破坏组装，而E-钙粘蛋白促进组装。钙粘蛋白被认为通过增强细胞间的接触而促进连接蛋白（Cxs）组装成间隙连接（GJs），然而参与这一过程的分子机制尚未被探索。我们研究了由Cx43组成的GJ在来自永生化和非转化大鼠肝上皮细胞的等基因克隆中的组装，所述肝上皮细胞表达上皮钙粘蛋白（E-Cad），其抑制肿瘤细胞的恶性行为，或神经元钙粘蛋白（N-Cad），其增强肿瘤细胞的侵袭性和运动性行为。我们发现N-cad表达减弱了Cx43组装成GJ，而E-Cad表达促进了组装。N-Cad的表达通过非网格蛋白依赖性途径引起Cx43的内吞作用来抑制GJ组装。通过shRNA敲除N-Cad恢复了GJ组装。当两种钙粘蛋白同时在同一细胞类型中表达时，GJ组装和拆卸同时发生。我们的研究结果表明，E-Cad和N-Cad对大鼠肝上皮细胞中Cx43组装成GJ具有相反的作用。这些发现意味着GJ组装和拆卸是下游目标的信号启动的E-Cad和N-Cad，分别，并可能提供一个可能的解释不同的作用，这些钙粘蛋白在调节细胞的运动性和侵袭在肿瘤的进展和侵袭。
E-cadherin and N-cadherin affect the assembly of connexin43 into gap junctions differentially. N-cadherin disrupts assembly by triggering endocytosis of connexin43, whereas E-cadherin facilitates the assembly. Cadherins have been thought to facilitate the assembly of connexins (Cxs) into gap junctions (GJs) by enhancing cell–cell contact, however the molecular mechanisms involved in this process have remained unexplored. We examined the assembly of GJs composed of Cx43 in isogenic clones derived from immortalized and nontransformed rat liver epithelial cells that expressed either epithelial cadherin (E-Cad), which curbs the malignant behavior of tumor cells, or neuronal cadherin (N-Cad), which augments the invasive and motile behavior of tumor cells. We found that N-cad expression attenuated the assembly of Cx43 into GJs, whereas E-Cad expression facilitated the assembly. The expression of N-Cad inhibited GJ assembly by causing endocytosis of Cx43 via a nonclathrin-dependent pathway. Knock down of N-Cad by ShRNA restored GJ assembly. When both cadherins were simultaneously expressed in the same cell type, GJ assembly and disassembly occurred concurrently. Our findings demonstrate that E-Cad and N-Cad have opposite effects on the assembly of Cx43 into GJs in rat liver epithelial cells. These findings imply that GJ assembly and disassembly are the down-stream targets of the signaling initiated by E-Cad and N-Cad, respectively, and may provide one possible explanation for the disparate role played by these cadherins in regulating cell motility and invasion during tumor progression and invasion.