A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells

Cell. 2006 May 5;125(3):535-48. doi: 10.1016/j.cell.2006.02.045.

Abstract

Using functional and proteomic screens of proteins that regulate the Cdc42 GTPase, we have identified a network of protein interactions that center around the Cdc42 RhoGAP Rich1 and organize apical polarity in MDCK epithelial cells. Rich1 binds the scaffolding protein angiomotin (Amot) and is thereby targeted to a protein complex at tight junctions (TJs) containing the PDZ-domain proteins Pals1, Patj, and Par-3. Regulation of Cdc42 by Rich1 is necessary for maintenance of TJs, and Rich1 is therefore an important mediator of this polarity complex. Furthermore, the coiled-coil domain of Amot, with which it binds Rich1, is necessary for localization to apical membranes and is required for Amot to relocalize Pals1 and Par-3 to internal puncta. We propose that Rich1 and Amot maintain TJ integrity by the coordinate regulation of Cdc42 and by linking specific components of the TJ to intracellular protein trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Cell Adhesion / physiology
  • Cell Line
  • Cell Polarity / physiology*
  • Dogs
  • Epithelial Cells / metabolism*
  • GTPase-Activating Proteins / chemistry
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Macromolecular Substances / metabolism
  • Membrane Proteins / metabolism*
  • Mice
  • Microfilament Proteins
  • NIH 3T3 Cells
  • Nerve Tissue Proteins
  • Nucleoside-Phosphate Kinase / metabolism
  • Protein Structure, Tertiary / physiology
  • Protein Transport / physiology
  • Signal Transduction / physiology
  • Tight Junction Proteins
  • Tight Junctions / metabolism*
  • cdc42 GTP-Binding Protein / metabolism*

Substances

  • AMOT protein, human
  • ARHGAP17 protein, human
  • Carrier Proteins
  • GTPase-Activating Proteins
  • Intercellular Signaling Peptides and Proteins
  • Macromolecular Substances
  • Membrane Proteins
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • PATJ protein, human
  • Pard3 protein, rat
  • Tight Junction Proteins
  • Nucleoside-Phosphate Kinase
  • MPP5 protein, human
  • cdc42 GTP-Binding Protein