The PX-RICS-14-3-3ζ/θ complex couples N-cadherin-β-catenin with dynein-dynactin to mediate its export from the endoplasmic reticulum

Abstract

We have recently shown that β-catenin-facilitated export of cadherins from the endoplasmic reticulum requires PX-RICS, a β-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-β-catenin complex to the microtubule-based molecular motor dynein-dynactin. Similar to knockdown of PX-RICS, knockdown of either 14-3-3ζor -θresulted in the disappearance of N-cadherin and β-catenin from the cellcell boundaries. Furthermore, we found that PX-RICS and 14-3-3ζ/θ are present in a large multiprotein complex that contains dynein-dynactin components as well as N-cadherin and θ-catenin. Both RNAi- and dynamitin-mediated inhibition of dyneindynactin function also led to the absence of N-cadherin and β-catenin at the cell-cell contact sites. Our results suggest that the PX-RICS-14-3-3ζ/θ complex links the N-cadherin-β-catenin cargo with the dynein-dynactin motor and thereby mediates its endoplasmic reticulum export. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.