Plakophilin 2 couples actomyosin remodeling to desmosomal plaque assembly via RhoA

Lisa M. Godsel, Adi D. Dubash, Amanda E. Bass-Zubek, Evangeline V. Amargo, Jodi L. Klessner, Ryan P. Hobbs, Xinyu Chen, Kathleen J. Green

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Plakophilin 2 (PKP2), an armadillo family member closely related to p120 catenin (p120ctn), is a constituent of the intercellular adhesive junction, the desmosome. We previously showed that PKP2 loss prevents the incorporation of desmosome precursors enriched in the plaque protein desmoplakin (DP) into newly forming desmosomes, in part by disrupting PKC-dependent regulation of DP assembly competence. On the basis of the observation that DP incorporation into junctions is cytochalasin D-sensitive, here we ask whether PKP2 may also contribute to actin-dependent regulation of desmosome assembly. We demonstrate that PKP2 knockdown impairs cortical actin remodeling after cadherin ligation, without affecting p120ctn expression or localization. Our data suggest that these defects result from the failure of activated RhoA to localize at intercellular interfaces after cell-cell contact and an elevation of cellular RhoA, stress fibers, and other indicators of contractile signaling in squamous cell lines and atrial cardiomyocytes. Consistent with these observations, RhoA activation accelerated DP redistribution to desmosomes during the first hour of junction assembly, whereas sustained RhoA activity compromised desmosome plaque maturation. Together with our previous findings, these data suggest that PKP2 may functionally link RhoA- and PKC-dependent pathways to drive actin reorganization and regulate DP-IF interactions required for normal desmosome assembly.

Original languageEnglish (US)
Pages (from-to)2844-2859
Number of pages16
JournalMolecular biology of the cell
Volume21
Issue number16
DOIs
StatePublished - Aug 15 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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