Lateral clustering of cadherin-4 without homophilic interaction: possible involvement in the concentration process at cell-cell adhesion sites as well as in the cell adhesion activity

Biochem Biophys Res Commun. 2000 Oct 5;276(3):1191-8. doi: 10.1006/bbrc.2000.3590.

Abstract

It is thought that the concentration of classic cadherins at cell-cell adhesion sites is essential for generating strong cell-cell adhesion activity, but the mechanism is not well understood. To clarify the structural basis of the concentration process and the cell adhesion activity, we constructed various mutants of cadherin-4 and examined the adhesion properties of the transfectants. A deletion mutant lacking the entire cytoplasmic domain had weak, but significant Ca(2+)-dependent cell adhesion activity. Interestingly, the deletion mutant showed intrinsic cluster formation in the absence of cell-cell adhesion, possible lateral cluster formation. The cytoplasmic domain-deleted cadherin-4 containing the mutation of Trp-2 to Ala, which is known to inhibit the strand dimer formation required for the cell-cell adhesion, retained the possible activity of lateral cluster formation, supporting this notion. These results suggest that the extracellular domain has intrinsic activity of lateral cluster formation. Indeed, deletion of a cadherin repeat in the extracellular domain significantly reduced or abolished the lateral cluster formation as well as the concentration of cadherin-4 at cell-cell contact sites and cell adhesion activity. When transfectants of the cytoplasmic domain-deleted cadherin-4 made cell-cell contact and formed intimate cell-cell adhesion, the lateral clusters of cadherin-4 initially gathered at cell-cell contact sites, and a smooth linear concentration was gradually formed along the cell-cell adhesion interface. The results suggest that the lateral cluster formation is involved in the concentration process of cadherin-4 at cell-cell adhesion sites, hence in the strong cell adhesion activity of cadherin-4 as well.

Publication types

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

MeSH terms

  • Amino Acid Substitution / genetics
  • Animals
  • Cadherins / chemistry
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Adhesion
  • Cell Aggregation
  • Cytoplasm / metabolism
  • Intercellular Junctions / chemistry*
  • Intercellular Junctions / metabolism*
  • L Cells
  • Mice
  • Models, Biological
  • Mutation / genetics
  • Protein Binding
  • Protein Structure, Tertiary
  • Repetitive Sequences, Amino Acid / genetics
  • Transfection

Substances

  • Cadherins
  • R-cadherin