Plakophilin-3 Binds the Membrane and Filamentous Actin without Bundling F-Actin

Jyoti Gupta, Erumbi S. Rangarajan, Regina B. Troyanovsky, Indrajyoti Indra, Sergey M. Troyanovsky*, Tina Izard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Plakophilin-3 is a ubiquitously expressed protein found widely in epithelial cells and is a critical component of desmosomes. The plakophilin-3 carboxy-terminal domain harbors nine armadillo repeat motifs with largely unknown functions. Here, we report the 5 Å cryogenic electron microscopy (cryoEM) structure of the armadillo repeat motif domain of plakophilin-3, one of the smaller cryoEM structures reported to date. We find that this domain is a monomer or homodimer in solution. In addition, using an in vitro actin co-sedimentation assay, we show that the armadillo repeat domain of plakophilin-3 directly interacts with F-actin. This feature, through direct interactions with actin filaments, could be responsible for the observed association of extra-desmosomal plakophilin-3 with the actin cytoskeleton directly attached to the adherens junctions in A431 epithelial cells. Further, we demonstrate, through lipid binding analyses, that plakophilin-3 can effectively be recruited to the plasma membrane through phosphatidylinositol-4,5-bisphosphate-mediated interactions. Collectively, we report on novel properties of plakophilin-3, which may be conserved throughout the plakophilin protein family and may be behind the roles of these proteins in cell–cell adhesion.

Original languageEnglish (US)
Article number9458
JournalInternational journal of molecular sciences
Issue number11
StatePublished - Jun 2023


  • actin cytoskeleton
  • armadillo
  • desmosomes
  • phosphatidylinositol 4,5-bisphosphate
  • plakophilin
  • plasma membrane

ASJC Scopus subject areas

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry


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