The non-muscle ADF/cofilin-1 controls sarcomeric actin filament integrity and force production in striated muscle laminopathies
Authors list
Nicolas Vignier Maria Chatzifrangkeskou Luca Pinton Hugo Wioland Thibaut Marais Mégane Lemaitre Caroline Le Dour Cécile Peccate Déborah Cardoso Alain Schmitt Wei Wu Maria-Grazia Biferi Naïra Naouar Coline Macquart Maud Beuvin Valérie Decostre Gisèle Bonne Guillaume Romet-Lemonne Howard J Worman Francesco Saverio Tedesco Antoine Jégou Antoine MuchirAbstract
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.
Journal details
Journal Cell Reports
Volume 36
Issue number 8
Pages 109601
Available online
Publication date
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Publisher website (DOI) 10.1016/j.celrep.2021.109601
Europe PubMed Central 34433058
Pubmed 34433058
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