New insights into the molecular basis of desmoplakin and desmin-related cardiomyopathies

Karine Lapouge, Lionel Fantao, Marie France Champliaud, Fabienne Jaunin, Miguel A. Frias, Bertrand Favre, Denise Paulin, Kathleen J. Green, Luca Borradori*

*Corresponding author for this work

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Desmosomes are intercellular adhesive complexes that anchor the intermediate filament cytoskeleton to the cell membrane in epithelia and cardiac muscle cells. The desmosomal component desmoplakin plays a key role in tethering various intermediate filament networks through its C-terminal plakin repeat domain. To gain better insight into the cytoskeletal organization of cardiomyocytes, we investigated the association of desmoplakin with desmin by cell transfection, yeast two-hybrid, and/or in vitro binding assays. The results indicate that the association of desmoplakin with desmin depends on sequences within the linker region and C-terminal extremity of desmoplakin, where the B and C subdomains contribute to efficient binding; a potentially phosphorylatable serine residue in the C-terminal extremity of desmoplakin affects its association with desmin; the interaction of desmoplakin with non-filamentous desmin requires sequences contained within the desmin C-terminal rod portion and tail domain in yeast, whereas in in vitro binding studies the desmin tail is dispensable for association; and mutations in either the C-terminus of desmoplakin or the desmin tail linked to inherited cardiomyopathy seem to impair desmoplakin-desmin interaction. These studies increase our understanding of desmoplakin-intermediate filament interactions, which are important for maintenance of cytoarchitecture in cardiomyocytes, and give new insights into the molecular basis of desmoplakin- and desmin-related human diseases.

Original languageEnglish (US)
Pages (from-to)4974-4985
Number of pages12
JournalJournal of cell science
Volume119
Issue number23
DOIs
StatePublished - Dec 1 2006

Keywords

  • Cardiomyocyte
  • Cardiomyopathy
  • Desmin
  • Desmoplakin
  • Intermediate filaments
  • Vimentin

ASJC Scopus subject areas

  • Cell Biology

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    Lapouge, K., Fantao, L., Champliaud, M. F., Jaunin, F., Frias, M. A., Favre, B., Paulin, D., Green, K. J., & Borradori, L. (2006). New insights into the molecular basis of desmoplakin and desmin-related cardiomyopathies. Journal of cell science, 119(23), 4974-4985. https://doi.org/10.1242/jcs.03255