Cell Reports (Aug 2021)
The non-muscle ADF/cofilin-1 controls sarcomeric actin filament integrity and force production in striated muscle laminopathies
- 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 Muchir
Affiliations
- Nicolas Vignier
- Sorbonne Université, INSERM, Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France
- Maria Chatzifrangkeskou
- Sorbonne Université, INSERM, Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France
- Luca Pinton
- Department of Cell and Developmental Biology, University College London, London, UK; Randall Centre for Cell and Molecular Biophysics, King’s College London, London, UK
- Hugo Wioland
- Université de Paris, CNRS, Institut Jacques Monod, 75013 Paris, France
- Thibaut Marais
- Sorbonne Université, INSERM, Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France
- Mégane Lemaitre
- Sorbonne Université, UMS28, Phénotypage du Petit Animal, Paris, France
- Caroline Le Dour
- Sorbonne Université, INSERM, Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France
- Cécile Peccate
- Sorbonne Université, INSERM, Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France
- Déborah Cardoso
- Sorbonne Université, INSERM, Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France
- Alain Schmitt
- Université de Paris, INSERM, CNRS, Institut Cochin, 75005 Paris, France
- Wei Wu
- Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA
- Maria-Grazia Biferi
- Sorbonne Université, INSERM, Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France
- Naïra Naouar
- Sorbonne Université, INSERM, Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France
- Coline Macquart
- Sorbonne Université, INSERM, Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France
- Maud Beuvin
- Sorbonne Université, INSERM, Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France
- Valérie Decostre
- Sorbonne Université, INSERM, Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France
- Gisèle Bonne
- Sorbonne Université, INSERM, Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France
- Guillaume Romet-Lemonne
- Université de Paris, CNRS, Institut Jacques Monod, 75013 Paris, France
- Howard J. Worman
- Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA
- Francesco Saverio Tedesco
- Department of Cell and Developmental Biology, University College London, London, UK; Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children, London, UK; The Francis Crick Institute, London, UK
- Antoine Jégou
- Université de Paris, CNRS, Institut Jacques Monod, 75013 Paris, France
- Antoine Muchir
- Sorbonne Université, INSERM, Institut de Myologie, Centre de Recherche en Myologie, 75013 Paris, France; Corresponding author
- Journal volume & issue
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Vol. 36,
no. 8
p. 109601
Abstract
Summary: 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.
