The head domain of plakophilin-1 binds to desmoplakin and enhances its recruitment to desmosomes. Implications for cutaneous disease

J Biol Chem. 1999 Jun 25;274(26):18145-8. doi: 10.1074/jbc.274.26.18145.

Abstract

The contribution of desmosomes to epidermal integrity is evident in the inherited blistering disorder associated with the absence of a functional gene for plakophilin-1. To define the function of plakophilin-1 in desmosome assembly, interactions among the desmosomal cadherins, desmoplakin, and the armadillo family members plakoglobin and plakophilin-1 were examined. In transient expression assays, plakophilin-1 formed complexes with a desmoplakin amino-terminal domain and enhanced its recruitment to cell-cell borders; this recruitment was not dependent on the equimolar expression of desmosomal cadherins. In contrast to desmoplakin-plakoglobin interactions, the interaction between desmoplakin and plakophilin-1 was not mediated by the armadillo repeat domain of plakophilin-1 but by the non-armadillo head domain, as assessed by yeast two-hybrid and recruitment assays. We propose a model whereby plakoglobin serves as a linker between the cadherins and desmoplakin, whereas plakophilin-1 enhances lateral interactions between desmoplakin molecules. This model suggests that epidermal lesions in patients lacking plakophilin-1 are a consequence of the loss of integrity resulting from a decrease in binding sites for desmoplakin and intermediate filaments at desmosomes.

Publication types

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

MeSH terms

  • Animals
  • COS Cells
  • Cell Adhesion Molecules / metabolism*
  • Cytoskeletal Proteins / metabolism*
  • Desmoplakins
  • Desmosomes / metabolism*
  • Plakophilins
  • Protein Binding
  • Protein Conformation
  • Proteins / metabolism*
  • Rabbits
  • Skin Diseases / physiopathology*
  • gamma Catenin

Substances

  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • Desmoplakins
  • Plakophilins
  • Proteins
  • gamma Catenin