Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2022.783724
Keywords
desmin; vinculin; focal adhesion; migration; myopathies; intermediate filaments
Categories
Funding
- Universite de Paris
- French National Center for Scientific Research (CNRS)
- Association Francaise Contre les Myopathies (AFM) [18358, 20802, 22142, 22956]
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This study reveals a novel role for desmin in cell-matrix adhesion, affecting focal adhesion area and adhesion-signaling gene expression. Knock-out and knock-in-p.R405W mice showed reduced adhesive abilities and increased migration speed of satellite cells. Mislocalization and aggregation of vinculin were observed in DesKO and DesKI-R405W muscles, and increased vinculin expression was found in desmin-related myopathy patient muscles.
Cellular adhesion and migration are key functions that are disrupted in numerous diseases. We report that desmin, a type-III muscle-specific intermediate filament, is a novel cell adhesion regulator. Expression of p.R406W mutant desmin, identified in patients with desmin-related myopathy, modified focal adhesion area and expression of adhesion-signaling genes in myogenic C2C12 cells. Satellite cells extracted from desmin-knock-out (DesKO) and desmin-knock-in-p.R405W (DesKI-R405W) mice were less adhesive and migrated faster than those from wild-type mice. Moreover, we observed mislocalized and aggregated vinculin, a key component of cell adhesion, in DesKO and DesKI-R405W muscles. Vinculin expression was also increased in desmin-related myopathy patient muscles. Together, our results establish a novel role for desmin in cell-matrix adhesion, an essential process for strength transmission, satellite cell migration and muscle regeneration. Our study links the patho-physiological mechanisms of desminopathies to adhesion/migration defects, and may lead to new cellular targets for novel therapeutic approaches.
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