Cofilin loss in Drosophila muscles contributes to muscle weakness through defective sarcomerogenesis during muscle growth Journal Article
| Authors: | Balakrishnan, M.; Yu, S. F.; Chin, S. M.; Soffar, D. B.; Windner, S. E.; Goode, B. L.; Baylies, M. K. |
| Article Title: | Cofilin loss in Drosophila muscles contributes to muscle weakness through defective sarcomerogenesis during muscle growth |
| Abstract: | How sarcomeres are added and maintained in a growing muscle cell is unclear. Balakrishnan et al. observed that DmCFL loss in growing muscles affects sarcomere size and addition through unregulated actin polymerization. This results in a collapse of sarcomere and muscle structure, formation of large protein aggregates, and muscle weakness. © 2020 The Authors Sarcomeres, the fundamental contractile units of muscles, are conserved structures composed of actin thin filaments and myosin thick filaments. How sarcomeres are formed and maintained is not well understood. Here, we show that knockdown of Drosophila cofilin (DmCFL), an actin depolymerizing factor, disrupts both sarcomere structure and muscle function. The loss of DmCFL also results in the formation of sarcomeric protein aggregates and impairs sarcomere addition during growth. The activation of the proteasome delays muscle deterioration in our model. Furthermore, we investigate how a point mutation in CFL2 that causes nemaline myopathy (NM) in humans affects CFL function and leads to the muscle phenotypes observed in vivo. Our data provide significant insights to the role of CFLs during sarcomere formation, as well as mechanistic implications for disease progression in NM patients. © 2020 The Authors |
| Keywords: | drosophila; skeletal muscle; muscle growth; cofilin; actin depolymerizing factor; nemaline myopathy; sarcomeres; actin thin filaments; sarcomere addition; sarcomere homeostasis |
| Journal Title: | Cell Reports |
| Volume: | 32 |
| Issue: | 3 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2020-07-21 |
| Start Page: | 107893 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2020.107893 |
| PUBMED: | 32697999 |
| PROVIDER: | scopus |
| PMCID: | PMC7479987 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 August 2020 -- Source: Scopus |
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