ArticleHuman molecular genetics2017
Novel nesprin-1 mutations associated with dilated cardiomyopathy cause nuclear envelope disruption and defects in myogenesis.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.
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Who cites it
66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 99 citations in OpenAlex.
- Cross-ancestry genome-wide analysis of atrial fibrillation unveils disease biology and enables cardioembolic risk prediction.Nature genetics · 2023Pooled it
- Pooled it
- Nuclear SUN2 coordinates endothelial cell-matrix interactions to regulate blood vessel homeostasis and barrier function.Angiogenesis · 2026Article
- NUAK1 Inhibition Alleviates Ischemia-Reperfusion Injury via SYNE1-YAP1.Circulation research · 2026Article
- Nuclear SUN2 coordinates endothelial cell-matrix interactions to regulate blood vessel homeostasis and barrier function.bioRxiv : the preprint server for biology · 2026Article
- Cargo Recognition of Nesprin-2 by the Dynein Adapter Bicaudal D2 for a Nuclear Positioning Pathway That Is Important for Brain Development.Biochemistry · 2026Article
- Exploring the Role of Nesprin1 in isoproterenol-induced heart failure: Insights into pathogenesis and therapeutic implications.PloS one · 2026Article
- Mechanical regulation of LINC complex function: structural basis, physiological roles, and disease mechanisms in transnuclear mechanotransduction.Frontiers in cell and developmental biology · 2026Review
- IntronicInternational journal of molecular sciences · 2025Article
- Role of Nuclear Envelope Proteins in the Structure and Function of the Neuromuscular Junction: Focus on Subsynaptic Nuclei.Sub-cellular biochemistry · 2025Review
- Nuclear envelope proteins, mechanotransduction, and their contribution to breast cancer progression.npj biological physics and mechanics · 2025Review
- Tail-anchored membrane protein SLMAP3 is essential for targeting centrosomal proteins to the nuclear envelope in skeletal myogenesis.Open biology · 2024Article
- The Drosophila Nesprin-1 homolog MSP300 is required for muscle autophagy and proteostasis.Journal of cell science · 2024Article
- Nesprin proteins: bridging nuclear envelope dynamics to muscular dysfunction.Cell communication and signaling : CCS · 2024Review
- Article
- Nucleus Mechanosensing in Cardiomyocytes.International journal of molecular sciences · 2023Review
- Caenorhabditis elegans models for striated muscle disorders caused by missense variants of human LMNA.PLoS genetics · 2023Article
- Nesprin-1: novel regulator of striated muscle nuclear positioning and mechanotransduction.Biochemical Society transactions · 2023Review
- Nuclear SUN1 stabilizes endothelial cell junctions via microtubules to regulate blood vessel formation.eLife · 2023Article
- Nesprin-1 LINC complexes recruit microtubule cytoskeleton proteins and drive pathology in Lmna-mutant striated muscle.Human molecular genetics · 2023Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 10 institutions in 5 countries.
Funding
Abstract
Nesprins-1 and -2 are highly expressed in skeletal and cardiac muscle and together with SUN (Sad1p/UNC84)-domain containing proteins and lamin A/C form the LInker of Nucleoskeleton-and-Cytoskeleton (LINC) bridging complex at the nuclear envelope (NE). Mutations in nesprin-1/2 have previously been found in patients with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD) as well as dilated cardiomyopathy (DCM). In this study, three novel rare variants (R8272Q, S8381C and N8406K) in the C-terminus of the SYNE1 gene (nesprin-1) were identified in seven DCM patients by mutation screening. Expression of these mutants caused nuclear morphology defects and reduced lamin A/C and SUN2 staining at the NE. GST pull-down indicated that nesprin-1/lamin/SUN interactions were disrupted. Nesprin-1 mutations were also associated with augmented activation of the ERK pathway in vitro and in hearts in vivo. During C2C12 muscle cell differentiation, nesprin-1 levels are increased concomitantly with kinesin light chain (KLC-1/2) and immunoprecipitation and GST pull-down showed that these proteins interacted via a recently identified LEWD domain in the C-terminus of nesprin-1. Expression of nesprin-1 mutants in C2C12 cells caused defects in myoblast differentiation and fusion associated with dysregulation of myogenic transcription factors and disruption of the nesprin-1 and KLC-1/2 interaction at the outer nuclear membrane. Expression of nesprin-1α2 WT and mutants in zebrafish embryos caused heart developmental defects that varied in severity. These findings support a role for nesprin-1 in myogenesis and muscle disease, and uncover a novel mechanism whereby disruption of the LINC complex may contribute to the pathogenesis of DCM.
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