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Rescue of mechanical function, muscle morphology and signaling by desmin plasmid transfection
Author(s) -
Lieber Richard Louis,
Palmisano Michelle,
Shah Sameer,
Hornberger Troy,
Ryan Allen F.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1218.1
Subject(s) - desmin , intermediate filament , transfection , microbiology and biotechnology , cytoskeleton , phosphorylation , myofibril , electroporation , chemistry , protein filament , biology , cell , biochemistry , immunology , gene , vimentin , immunohistochemistry
The muscle‐specific intermediate filament desmin has been described as the “mechanical integrator” of the muscle cell. We probed this function by transfecting adult desmin knockout (DKO) muscle with plasmid DNA encoding desmin and measuring the resulting structural and functional changes. Mice were transfected by electroporation and, after 7 days, when protein expression peaked, we measured the regularity of the myofibrillar lattice and several responses to mechanical stretch including the deformability of nuclei, stress production, injury and c‐Jun‐kinase (JNK) phosphorylation. Desmin transfection reversed essentially all of the knockout phenotype in a quantitative manner—Z‐disks were re‐aligned, myonuclear deformability was restored, and stress production and the resulting injury response was also returned to near‐wildtype levels in a dose‐dependent, although nonlinear manner. Furthermore, the stretch‐induced activation of JNK phosphorylation, which was not detectable in the DKO muscles, was restored. These results demonstrate that the desmin intermediate filament is primarily responsible for the spatial alignment of Z‐disks and plays a central role in transducing mechanical stress: (1) from the force‐generating cytoskeletal network to the surrounding tissue and (2) to the intracellular signaling apparatus. Supported by NIH and Department of Veterans Affairs.