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The amino-terminal domain of desmoplakin binds to plakoglobin and clusters desmosomal cadherin-plakoglobin complexes.

The desmosome is a highly organized plasma membrane domain that couples intermediate filaments to the plasma membrane at regions of cell-cell adhesion. Desmosomes contain two classes of cadherins, desmogleins, and desmocollins, that bind to the cytoplasmic protein plakoglobin. Desmoplakin is a desmosomal component that plays a critical role in linking intermediate filament networks to the desmosomal plaque, and the amino-terminal domain of desmoplakin targets desmoplakin to the desmosome. However, the desmosomal protein(s) that bind the amino-terminal domain of desmoplakin have not been identified. To determine if the desmosomal cadherins and plakoglobin interact with the amino-terminal domain of desmoplakin, these proteins were co-expressed in L-cell fibroblasts, cells that do not normally express desmosomal components. When expressed in L-cells, the desmosomal cadherins and plakoglobin exhibited a diffuse distribution. However, in the presence of an amino-terminal desmoplakin polypeptide (DP-NTP), the desmosomal cadherins and plakoglobin were observed in punctate clusters that also contained DP-NTP. In addition, plakoglobin and DP-NTP were recruited to cell-cell interfaces in L-cells co-expressing a chimeric cadherin with the E-cadherin extracellular domain and the desmoglein-1 cytoplasmic domain, and these cells formed structures that were ultrastructurally similar to the outer plaque of the desmosome. In transient expression experiments in COS cells, the recruitment of DP-NTP to cell borders by the chimera required co-expression of plakoglobin. Plakoglobin and DP-NTP co-immunoprecipitated when extracted from L-cells, and yeast two hybrid analysis indicated that DP-NTP binds directly to plakoglobin but not Dsg1. These results identify a role for desmoplakin in organizing the desmosomal cadherin-plakoglobin complex and provide new insights into the hierarchy of protein interactions that occur in the desmosomal plaque.

Pubmed ID: 9348293

Authors

  • Kowalczyk AP
  • Bornslaeger EA
  • Borgwardt JE
  • Palka HL
  • Dhaliwal AS
  • Corcoran CM
  • Denning MF
  • Green KJ

Journal

The Journal of cell biology

Publication Data

November 3, 1997

Associated Grants

  • Agency: NIAMS NIH HHS, Id: R01AR41836
  • Agency: NIAMS NIH HHS, Id: R01AR43380

Mesh Terms

  • Animals
  • Cadherins
  • Cytoplasm
  • Cytoskeletal Proteins
  • Desmocollins
  • Desmoglein 1
  • Desmogleins
  • Desmoplakins
  • Desmosomes
  • Extracellular Space
  • Humans
  • L Cells (Cell Line)
  • Macromolecular Substances
  • Mice
  • Peptides
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins
  • alpha Catenin
  • gamma Catenin