Desmoplakin interacts with the coil 1 of different types of intermediate filament proteins and displays high affinity for assembled intermediate filaments | Academic Article individual record
abstract

The interaction of intermediate filaments (IFs) with the cell-cell adhesion complexes desmosomes is crucial for cytoskeletal organization and cell resilience in the epidermis and heart. The intracellular desmosomal protein desmoplakin anchors IFs to the cell adhesion complexes predominantly via its four last carboxy-terminal domains (C-terminus). However, it remains unclear why the C-terminus of desmoplakin interacts with different IF types or if there are different binding affinities for each type of IFs that may influence the stability of cell-specific adhesion complexes. By yeast three-hybrid and fluorescence binding assays, we found that the coiled-coil 1 of the conserved central rod domain of the heterodimeric cytokeratins (Ks) 5 and 14 (K5/K14) was required for their interaction with the C-terminus of desmoplakin, while their unique amino head- and C-tail domains were dispensable. Similar findings were obtained in vitro with K1/K10, and the type III IF proteins desmin and vimentin. Binding assays testing the C-terminus of desmoplakin with assembled K5/K14 and desmin IFs yielded an apparent affinity in the nM range. Our findings reveal that the same conserved domain of IF proteins binds to the C-terminus of desmoplakin, which may help explain the previously reported broad binding IF-specificity to desmoplakin. Our data suggest that desmoplakin high-affinity binding to diverse IF proteins ensures robust linkages of IF cytoskeleton and desmosomes that maintain the structural integrity of cellular adhesion complexes. In summary, our results give new insights into the molecular basis of the IF-desmosome association.

author list (cited authors)
Favre, B., Begré, N., Bouameur, J., Lingasamy, P., Conover, G. M., Fontao, L., & Borradori, L.
publication date
2018
published in
PLoS ONE Journal
keywords
  • Desmoplakins
  • Intermediate Filaments
  • Intermediate Filament Proteins
  • HEK293 Cells
  • Sequence Alignment
  • Protein Binding
  • Binding Sites
  • Humans