Next Article in Journal
Extracellular Vesicles in NAFLD/ALD: From Pathobiology to Therapy
Previous Article in Journal
Redox Modifications of Proteins of the Mitochondrial Fusion and Fission Machinery
 
 
Article

Lamin Mutations Cause Increased YAP Nuclear Entry in Muscle Stem Cells

1
INSERM UMRS_974, Centre for Research in Myology, Sorbonne Université, 75013 Paris, France
2
Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool L3 3AF, UK
3
Inovarion, 75013 Paris, France
4
Association Institut de Myology, 75013 Paris, France
*
Author to whom correspondence should be addressed.
Cells 2020, 9(4), 816; https://doi.org/10.3390/cells9040816
Received: 26 February 2020 / Revised: 24 March 2020 / Accepted: 24 March 2020 / Published: 27 March 2020
(This article belongs to the Section Cell Nuclei: Function, Transport and Receptors)
Mutations in the LMNA gene, encoding the nuclear envelope A-type lamins, are responsible for muscular dystrophies, the most severe form being the LMNA-related congenital muscular dystrophy (L-CMD), with severe defects in myonucleus integrity. We previously reported that L-CMD mutations compromise the ability of muscle stem cells to modulate the yes-associated protein (YAP), a pivotal factor in mechanotransduction and myogenesis. Here, we investigated the intrinsic mechanisms by which lamins influence YAP subcellular distribution, by analyzing different conditions affecting the balance between nuclear import and export of YAP. In contrast to wild type (WT) cells, LMNADK32 mutations failed to exclude YAP from the nucleus and to inactivate its transcriptional activity at high cell density, despite activation of the Hippo pathway. Inhibiting nuclear pore import abolished YAP nuclear accumulation in confluent mutant cells, thus showing persistent nuclear import of YAP at cell confluence. YAP deregulation was also present in congenital myopathy related to nesprin-1 KASH mutation, but not in cells expressing the LMNAH222P mutation, the adult form of lamin-related muscle dystrophy with reduced nuclear deformability. In conclusion, our data showed that L-CMD mutations increased YAP nuclear localization via an increased nuclear import and implicated YAP as a pathogenic contributor in muscle dystrophies caused by nuclear envelop defects. View Full-Text
Keywords: lamins; congenital myopathy; nucleo-cytoskeletal translocation; nuclear envelope lamins; congenital myopathy; nucleo-cytoskeletal translocation; nuclear envelope
Show Figures

Figure 1

MDPI and ACS Style

Owens, D.J.; Fischer, M.; Jabre, S.; Moog, S.; Mamchaoui, K.; Butler-Browne, G.; Coirault, C. Lamin Mutations Cause Increased YAP Nuclear Entry in Muscle Stem Cells. Cells 2020, 9, 816. https://doi.org/10.3390/cells9040816

AMA Style

Owens DJ, Fischer M, Jabre S, Moog S, Mamchaoui K, Butler-Browne G, Coirault C. Lamin Mutations Cause Increased YAP Nuclear Entry in Muscle Stem Cells. Cells. 2020; 9(4):816. https://doi.org/10.3390/cells9040816

Chicago/Turabian Style

Owens, Daniel J., Martina Fischer, Saline Jabre, Sophie Moog, Kamel Mamchaoui, Gillian Butler-Browne, and Catherine Coirault. 2020. "Lamin Mutations Cause Increased YAP Nuclear Entry in Muscle Stem Cells" Cells 9, no. 4: 816. https://doi.org/10.3390/cells9040816

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop