| First Author | Vignier N | Year | 2021 |
| Journal | Cell Rep | Volume | 36 |
| Issue | 8 | Pages | 109601 |
| PubMed ID | 34433058 | Mgi Jnum | J:320608 |
| Mgi Id | MGI:6876880 | Doi | 10.1016/j.celrep.2021.109601 |
| Citation | Vignier N, et al. (2021) The non-muscle ADF/cofilin-1 controls sarcomeric actin filament integrity and force production in striated muscle laminopathies. Cell Rep 36(8):109601 |
| abstractText | Cofilins are important for the regulation of the actin cytoskeleton, sarcomere organization, and force production. The role of cofilin-1, the non-muscle-specific isoform, in muscle function remains unclear. Mutations in LMNA encoding A-type lamins, intermediate filament proteins of the nuclear envelope, cause autosomal Emery-Dreifuss muscular dystrophy (EDMD). Here, we report increased cofilin-1 expression in LMNA mutant muscle cells caused by the inability of proteasome degradation, suggesting a protective role by ERK1/2. It is known that phosphorylated ERK1/2 directly binds to and catalyzes phosphorylation of the actin-depolymerizing factor cofilin-1 on Thr25. In vivo ectopic expression of cofilin-1, as well as its phosphorylated form on Thr25, impairs sarcomere structure and force generation. These findings present a mechanism that provides insight into the molecular pathogenesis of muscular dystrophies caused by LMNA mutations. |
