EGF induces macropinocytosis and SNX1-modulated recycling of E-cadherin

J Cell Sci. 2007 May 15;120(Pt 10):1818-28. doi: 10.1242/jcs.000653.

Abstract

In epithelia, junction proteins are endocytosed for modulation of cell-cell adhesion and cell polarity. In response to growth factors, the cell-cell adhesion protein E-cadherin is internalized from the cell surface with degradation or recycling as potential fates. However, the cellular machinery involved in cadherin internalization and recycling remains controversial. Here we investigated EGF-induced E-cadherin internalization. EGF stimulation of MCF-7 cells resulted in Rac1-modulated macropinocytosis of the E-cadherin-catenin complex into endosomal compartments that colocalized with EEA1 and the sorting nexin, SNX1. Depletion of cellular SNX1 levels by siRNA resulted in increased intracellular accumulation and turnover of E-cadherin internalized from the cell surface in response to EGF. Moreover, SNX1 was also required for efficient recycling of internalized E-cadherin and re-establishment of epithelial adhesion. Together, these findings demonstrate a role for SNX1 in retrieval of E-cadherin from a degradative endosomal pathway and in membrane trafficking pathways that regulate E-cadherin recycling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / metabolism*
  • Cell Line, Tumor
  • Endocytosis / physiology
  • Endosomes / metabolism
  • Epidermal Growth Factor / metabolism*
  • Epidermal Growth Factor / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Epithelial Cells / ultrastructure
  • Humans
  • Intercellular Junctions / metabolism*
  • Membrane Proteins / metabolism
  • Pinocytosis / drug effects
  • Pinocytosis / physiology*
  • Protein Transport / physiology
  • RNA, Small Interfering
  • Signal Transduction / physiology
  • Sorting Nexins
  • Transport Vesicles / metabolism
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*
  • rac1 GTP-Binding Protein / metabolism

Substances

  • Cadherins
  • Membrane Proteins
  • RNA, Small Interfering
  • SNX1 protein, human
  • Sorting Nexins
  • Vesicular Transport Proteins
  • early endosome antigen 1
  • Epidermal Growth Factor
  • rac1 GTP-Binding Protein