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Regulation of cadherin function by Rho and Rac: modulation by junction maturation and cellular context

V M Braga1, A Del Maschio, L Machesky

  • 1MRC-Laboratory for Molecular Cell Biology, University College London, WC1E 6BT, London, United Kingdom.

Molecular Biology of the Cell
|January 8, 1999
PubMed
Summary

Small GTPases Rho and Rac regulate E-cadherin adhesion in keratinocytes, but not VE-cadherin in endothelial cells. Their impact depends on junction maturity and cell type, highlighting complex regulation of cell-cell adhesion.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cadherins mediate cell-cell adhesion, requiring linkage to the actin cytoskeleton via catenins.
  • Small GTPases Rho and Rac control distinct actin structures and are crucial for E-cadherin function in epithelial cells.

Purpose of the Study:

  • To investigate how the maturation status of cell junctions and cellular context influence the regulation of cadherin adhesiveness by Rho and Rac.
  • To determine the differential roles of Rho/Rac in E-cadherin, P-cadherin, and VE-cadherin localization and function.

Main Methods:

  • Inhibition of Rho and Rac GTPases in keratinocytes and endothelial cells.
  • Analysis of E-cadherin, P-cadherin, and VE-cadherin localization in mature and newly formed cell junctions.
  • Transfection of VE-cadherin into CHO cells to assess cellular context effects.

Related Experiment Videos

Main Results:

  • Rho and Rac inhibition disrupted E-cadherin localization in mature keratinocyte junctions after a 2-hour delay, but not in newly formed contacts.
  • P-cadherin was removed from mature keratinocyte junctions upon Rho or Rac inhibition.
  • VE-cadherin localization in endothelial cells was independent of Rho/Rac activity, unlike its behavior when transfected into CHO cells.

Conclusions:

  • Cadherin regulation by Rho and Rac is context-dependent, varying with junction maturity and cell type.
  • VE-cadherin localization in endothelial cells is distinct from epithelial cadherins regarding Rho/Rac dependency.
  • Rho and Rac play roles in establishing E-cadherin contacts, but cadherin redistribution primarily relies on homophilic receptor binding.