Article: article from journal or magazin.
New insights into the molecular basis of desmoplakin- and desmin-related cardiomyopathies.
Journal of Cell Science
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 desmoplakindesmin 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.
Animals, Animals, Newborn, Cardiomyopathies/genetics, Cells, Cultured, Desmin/genetics, Desmin/metabolism, Desmoplakins/genetics, Desmoplakins/metabolism, Humans, Mutant Proteins/metabolism, Mutation, Myocytes, Cardiac/metabolism, Protein Binding, Protein Structure, Tertiary, Rats, Rats, Wistar, Sequence Analysis, Protein, Tissue Distribution, Transfection, Two-Hybrid System Techniques
Web of science
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