The PX-RICS-14-3-3ζ/θ Complex Couples N-cadherin-β-Catenin with Dynein-Dynactin to Mediate Its Export from the Endoplasmic Reticulum
The PX-RICS-14-3-3ζ/θ Complex Couples N-cadherin-β-Catenin with Dynein-Dynactin to Mediate Its Export from the Endoplasmic Reticulum
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DOI：
10.1074/jbc.m109.081315
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发表时间：
2010-05-21
影响因子：
4.8
通讯作者：
Akiyama, Tetsu
中科院分区：
文献类型：
--
作者：
Nakamura, Tsutomu;Hayashi, Tomoatsu;Akiyama, Tetsu
我们最近的研究表明，β-连环蛋白促进的钙粘蛋白从内质网的出口需要PX-RICS，一种β-连环蛋白相互作用的GTP酶激活蛋白Cdc 42。在这里，我们表明，PX-RICS与14-3-3的异构体相互作用，并将N-钙粘蛋白-β-连环蛋白复合物偶联到基于微管的分子马达动力蛋白-动力蛋白。类似于PX-RICS的敲低，14-3-3 ζ或-θ的敲低导致N-钙粘蛋白和β-连环蛋白从细胞-细胞边界消失。此外，我们发现PX-RICS和14-3-3 zeta/theta存在于一个大的多蛋白复合物中，该复合物含有动力蛋白-动力蛋白组分以及N-钙粘蛋白和β-连环蛋白。RNAi和dynamitin介导的动力蛋白-动力肌动蛋白功能的抑制也导致细胞-细胞接触位点的N-钙粘蛋白和β-连环蛋白的缺失。我们的研究结果表明，PX-RICS-14-3-3 zeta/theta复合物连接N-钙粘蛋白-β-连环蛋白货物与动力蛋白-动力蛋白马达，从而介导其内质网输出。
We have recently shown that beta-catenin-facilitated export of cadherins from the endoplasmic reticulum requires PX-RICS, a beta-catenin-interacting GTPase-activating protein for Cdc42. Here we show that PX-RICS interacts with isoforms of 14-3-3 and couples the N-cadherin-beta-catenin complex to the microtubule-based molecular motor dynein-dynactin. Similar to knockdown of PX-RICS, knockdown of either 14-3-3 zeta or -theta resulted in the disappearance of N-cadherin and beta-catenin from the cell-cell boundaries. Furthermore, we found that PX-RICS and 14-3-3 zeta/theta are present in a large multiprotein complex that contains dynein-dynactin components as well as N-cadherin and beta-catenin. Both RNAi- and dynamitin-mediated inhibition of dynein-dynactin function also led to the absence of N-cadherin and beta-catenin at the cell-cell contact sites. Our results suggest that the PX-RICS-14-3-3 zeta/theta complex links the N-cadherin-beta-catenin cargo with the dynein-dynactin motor and thereby mediates its endoplasmic reticulum export.