Vignier, N;
Chatzifrangkeskou, M;
Pinton, L;
Wioland, H;
Marais, T;
Lemaitre, M;
Le Dour, C;
... Muchir, A; + view all
(2021)
The non-muscle ADF/cofilin-1 controls sarcomeric actin filament integrity and force production in striated muscle laminopathies.
Cell Reports
, 36
(8)
, Article 109601. 10.1016/j.celrep.2021.109601.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | The non-muscle ADF/cofilin-1 controls sarcomeric actin filament integrity and force production in striated muscle laminopathies |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2021.109601 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2021.109601 |
| Language: | English |
| Additional information: | ©2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | cofilin-1, ERK1/2 signaling, muscular dystrophy, skeletal muscle, sarcomeric organization |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10133942 |
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