ArticleCardiovascular research2023
Lem2 is essential for cardiac development by maintaining nuclear integrity.
Article in Cardiovascular research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Nuclear mechanobiology: a brief history and five unresolved questions.Nucleus (Austin, Tex.) · 2026Article
- The nucleus as a mechanobiological hub in muscle aging.Nucleus (Austin, Tex.) · 2026Review
- Nuclear envelope rupture and resealing: mechanisms, consequences, and disease implications.Biochemical Society transactions · 2026Review
- Systematic Analysis of MRTFB Phosphoproteomic Datasets Reveals Co-Regulated Kinase Networks and Co-Occurring Phosphosites Associated with the Actin Cytoskeleton Pathway.Current issues in molecular biology · 2026Article
- Transformative biomechanics and mechanobiology breakthroughs shaping the future of health and medicine.Innovation (Cambridge (Mass.)) · 2026Review
- LEM-Domain-Containing Inner Nuclear Membrane Proteins: Emerging Regulators of Intranuclear Signaling.International journal of molecular sciences · 2026Review
- Measuring age-dependent viscoelasticity of organelles, cells and organisms with time-shared optical tweezer microrheology.Nature nanotechnology · 2025Article
- A novel role for CSA in the regulation of nuclear envelope integrity: uncovering a non-canonical function.Life science alliance · 2024Article
- LEMD2-associated progeroid syndrome: Expanding the phenotype of the nuclear envelopathy caused by a defect in LEMD2 gene.Aging cell · 2024Article
- Pervasive nuclear envelope ruptures precede ECM signaling and disease onset without activating cGAS-STING in Lamin-cardiomyopathy mice.Cell reports · 2024Article
- Pervasive nuclear envelope ruptures precede ECM signaling and disease onset without activating cGAS-STING in Lamin-cardiomyopathy mice.bioRxiv : the preprint server for biology · 2024Article
- The dynamic nuclear envelope: resilience in health and dysfunction in disease.Current opinion in cell biology · 2023Review
- Quantitative Image Processing for Three-Dimensional Episcopic Images of Biological Structures: Current State and Future Directions.Biomedicines · 2023Review
- Altered Expression ofInternational journal of molecular sciences · 2022Article
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
aimsNuclear envelope integrity is essential for the compartmentalization of the nucleus and cytoplasm. Importantly, mutations in genes encoding nuclear envelope (NE) and associated proteins are the second highest cause of familial dilated cardiomyopathy. One such NE protein that causes cardiomyopathy in humans and affects mouse heart development is Lem2. However, its role in the heart remains poorly understood. METHODS AND
resultsWe generated mice in which Lem2 was specifically ablated either in embryonic cardiomyocytes (Lem2 cKO) or in adult cardiomyocytes (Lem2 iCKO) and carried out detailed physiological, tissue, and cellular analyses. High-resolution episcopic microscopy was used for three-dimensional reconstructions and detailed morphological analyses. RNA-sequencing and immunofluorescence identified altered pathways and cellular phenotypes, and cardiomyocytes were isolated to interrogate nuclear integrity in more detail. In addition, echocardiography provided a physiological assessment of Lem2 iCKO adult mice. We found that Lem2 was essential for cardiac development, and hearts from Lem2 cKO mice were morphologically and transcriptionally underdeveloped. Lem2 cKO hearts displayed high levels of DNA damage, nuclear rupture, and apoptosis. Crucially, we found that these defects were driven by muscle contraction as they were ameliorated by inhibiting myosin contraction and L-type calcium channels. Conversely, reducing Lem2 levels to ∼45% in adult cardiomyocytes did not lead to overt cardiac dysfunction up to 18 months of age.
conclusionsOur data suggest that Lem2 is critical for integrity at the nascent NE in foetal hearts, and protects the nucleus from the mechanical forces of muscle contraction. In contrast, the adult heart is not detectably affected by partial Lem2 depletion, perhaps owing to a more established NE and increased adaptation to mechanical stress. Taken together, these data provide insights into mechanisms underlying cardiomyopathy in patients with mutations in Lem2 and cardio-laminopathies in general.
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