Desmoglein 3 acting as an upstream regulator of Rho GTPases, Rac-1/Cdc42 in the regulation of actin organisation and dynamics

Siu Man Tsang, Louise Brown, Hanan Gadmor, Luke Gammon, Farida Fortune, Ann Wheeler, Hong Wan

Research output: Contribution to journalArticlepeer-review

Abstract

Desmoglein 3 (Dsg3), a member of the desmoglein sub-family, serves as an adhesion molecule in desmosomes. Our previous study showed that overexpression of human Dsg3 in several epithelial lines induces formation of membrane protrusions, a phenotype suggestive of Rho GTPase activation. Here we examined the interaction between Dsg3 and actin in detail and showed that endogenous Dsg3 colocalises and interacts with actin, particularly the junctional actin in a Rac1-dependent manner. Ablation of Rac1 activity by dominant negative Rac1 mutant (N17Rac1) or the Rac1 specific inhibitor (NSC23766) directly disrupts the interaction between Dsg3 and actin. Assembly of the junctional actin at the cell borders is accompanied with enhanced levels of Dsg3, while inhibition of Dsg3 by RNAi results in profound changes in the organisation of actin cytoskeleton. In accordance, overexpression of Dsg3 results in a remarkable increase of Rac1 and Cdc42 activities and to a lesser extent, RhoA. The enhancements in Rho GTPases are accompanied by the pronounced actin-based membrane structures such as lamellipodia and filopodia, enhanced rate of actin turnover and cell polarisation. Together, our results reveal an important novel function for Dsg3 in promoting actin dynamics through regulating Rac1 and Cdc42 activation in epithelial cells.

Original languageEnglish
Pages (from-to)2269-83
Number of pages15
JournalExperimental Cell Research
Volume318
Issue number18
DOIs
Publication statusPublished - 1 Nov 2012

Keywords

  • Actin Cytoskeleton
  • Actins
  • Cell Line
  • Cell Line, Tumor
  • Desmoglein 3
  • Epithelial Cells
  • Humans
  • Intercellular Junctions
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein

Fingerprint Dive into the research topics of 'Desmoglein 3 acting as an upstream regulator of Rho GTPases, Rac-1/Cdc42 in the regulation of actin organisation and dynamics'. Together they form a unique fingerprint.

Cite this