PX-RICS mediates ER-to-Golgi transport of the N-cadherin/beta-catenin complex

Genes Dev. 2008 May 1;22(9):1244-56. doi: 10.1101/gad.1632308.


Cadherins mediate Ca2+-dependent cell-cell adhesion. Efficient export of cadherins from the endoplasmic reticulum (ER) is known to require complex formation with beta-catenin. However, the molecular mechanisms underlying this requirement remain elusive. Here we show that PX-RICS, a beta-catenin-interacting GTPase-activating protein (GAP) for Cdc42, mediates ER-to-Golgi transport of the N-cadherin/beta-catenin complex. Knockdown of PX-RICS expression induced the accumulation of the N-cadherin/beta-catenin complex in the ER and ER exit site, resulting in a decrease in cell-cell adhesion. PX-RICS was also required for ER-to-Golgi transport of the fibroblast growth factor-receptor 4 (FGFR4) associated with N-cadherin. PX-RICS-mediated ER-to-Golgi transport was dependent on its interaction with beta-catenin, phosphatidylinositol-4-phosphate (PI4P), Cdc42, and its novel binding partner gamma-aminobutyric acid type A receptor-associated protein (GABARAP). These results suggest that PX-RICS ensures the efficient entry of the N-cadherin/beta-catenin complex into the secretory pathway, and thereby regulates the amount of N-cadherin available for cell adhesion and FGFR4-mediated signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis Regulatory Proteins
  • Cadherins / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Cells, Cultured
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Golgi Apparatus / metabolism*
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Knockout
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Phosphatidylinositol Phosphates / metabolism
  • Protein Binding
  • Protein Transport
  • RNA Interference
  • Receptor, Fibroblast Growth Factor, Type 4 / metabolism
  • Signal Transduction
  • beta Catenin / metabolism*
  • cdc42 GTP-Binding Protein / metabolism


  • ARHGAP32 protein, human
  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Cadherins
  • GABARAP protein, human
  • GABARAPL1 protein, human
  • GC-GAP protein, mouse
  • GTPase-Activating Proteins
  • Microtubule-Associated Proteins
  • Phosphatidylinositol Phosphates
  • beta Catenin
  • phosphatidylinositol 4-phosphate
  • FGFR4 protein, human
  • Receptor, Fibroblast Growth Factor, Type 4
  • cdc42 GTP-Binding Protein