期刊
JOURNAL OF CELL SCIENCE
卷 129, 期 9, 页码 1781-1791出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.184309
关键词
C. elegans; Emerin; Laminopathy; LINC complex; Mechanical strain; Nuclear envelope; Muscular dystrophy
类别
资金
- United States - Israel Binational Science Foundation [2007215]
- Muscular Dystrophy Association
- Niedersachsen-Israeli Research Cooperation
- German Israel Foundation
- Israel Science Foundation
- European Cooperation in Science and Technology (COST) [BM1002]
- Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) [SNSF 31003A_141083/1]
- European Molecular Biology Organization
There are roughly 14 distinct heritable autosomal dominant diseases associated with mutations in lamins A/C, including Emery-Dreifuss muscular dystrophy (EDMD). The mechanical model proposes that the lamin mutations change the mechanical properties of muscle nuclei, leading to cell death and tissue deterioration. Here, we developed an experimental protocol that analyzes the effect of disease-linked lamin mutations on the response of nuclei to mechanical strain in living Caenorhabditis elegans. We found that the EDMD mutation L535P disrupts the nuclear mechanical response specifically in muscle nuclei. Inhibiting lamin prenylation rescued the mechanical response of the EDMD nuclei, reversed the muscle phenotypes and led to normal motility. The LINC complex and emerin were also required to regulate the mechanical response of C. elegans nuclei. This study provides evidence to support the mechanical model and offers a potential future therapeutic approach towards curing EDMD.
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