Control of intracellular movement of connexins by E-cadherin in murine skin papilloma cells

Exp Cell Res. 2001 Nov 1;270(2):235-47. doi: 10.1006/excr.2001.5342.


The gap junctional intercellular communication-deficient mouse skin papilloma cell line P3/22 expresses Cx43 but not E-cadherin. The E-cadherin gene-transfected cells (P3E1) communicate in a calcium-dependent manner and they were used to study how E-cadherin restores the function of connexins. At low calcium, Cx43 molecules remain in the cytoplasm of P3E1 cells and appear at cell-cell contact areas only in high-calcium medium. While Cx43 is unphosphorylated in P3E1 cells in low-calcium medium, two phosphorylated bands appeared at high calcium. However, when Cx26, which has no C-terminal tail that can undergo phosphorylation, was expressed in P3E1 cells, this connexin also moved to the plasma membrane after the calcium shift and partly colocalized with Cx43, suggesting that C-terminal phosphorylation is not essential for E-cadherin-mediated intracellular transport of connexins. In low calcium, both Cx26 and Cx43 remained and colocalized in the endoplasmic reticulum. As early as 30 min after the shift to high-calcium medium, both Cx43 and Cx26 began to accumulate in the Golgi apparatus. Intracellular movement of connexins to the cytoplasmic membrane at high calcium was effectively blocked by cytochalasin D and brefeldin A. These results suggest that E-cadherin junction formation at high calcium leads to formation of actin cables, which directly or indirectly transport connexins from the cytoplasm to the cell-cell contact membranes via the Golgi apparatus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Adherens Junctions / chemistry
  • Adherens Junctions / metabolism
  • Adherens Junctions / ultrastructure
  • Animals
  • Cadherins / analysis
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Calcium / pharmacology
  • Cell Adhesion / physiology
  • Cell Communication / physiology
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Connexin 26
  • Connexin 43 / analysis
  • Connexin 43 / metabolism*
  • Connexins / metabolism
  • Culture Media / pharmacology
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum / ultrastructure
  • Gap Junctions / chemistry
  • Gap Junctions / metabolism
  • Gap Junctions / ultrastructure
  • Golgi Apparatus / metabolism
  • Golgi Apparatus / ultrastructure
  • Mice
  • Microscopy, Immunoelectron
  • Papilloma*
  • Skin Neoplasms*
  • Transfection
  • Tumor Cells, Cultured


  • Actins
  • Cadherins
  • Connexin 43
  • Connexins
  • Culture Media
  • Connexin 26
  • Calcium