ArticleCell communication and signaling : CCS2013
Mena/VASP and αII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy.
Article in Cell communication and signaling : CCS, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Considering impact of age and sex on cardiac cytoskeletal components.American journal of physiology. Heart and circulatory physiology · 2024Review
- MEK1-ERK1/2 signaling regulates the cardiomyocyte non-sarcomeric actin cytoskeletal network.American journal of physiology. Heart and circulatory physiology · 2024Article
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- Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse.Open life sciences · 2022Article
- Regulation of Cardiac Conduction and Arrhythmias by Ankyrin/Spectrin-Based Macromolecular Complexes.Journal of cardiovascular development and disease · 2021Review
- EVL regulates VEGF receptor-2 internalization and signaling in developmental angiogenesis.EMBO reports · 2021Article
- βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases.International journal of biological sciences · 2021Review
- Spectrin couples cell shape, cortical tension, and Hippo signaling in retinal epithelial morphogenesis.The Journal of cell biology · 2020Article
- RNA binding protein 24 deletion disrupts global alternative splicing and causes dilated cardiomyopathy.Protein & cell · 2019Article
- Supporting the heart: Functions of the cardiomyocyte's non-sarcomeric cytoskeleton.Journal of molecular and cellular cardiology · 2019Review
- Intercalated discs: cellular adhesion and signaling in heart health and diseases.Heart failure reviews · 2019Review
- Upregulation of Myocardial and Vascular Phosphodiesterase 9A in A Model of Atherosclerotic Cardiovascular Disease.International journal of molecular sciences · 2018Article
- Actin-associated proteins and cardiomyopathy-the 'unknown' beyond troponin and tropomyosin.Biophysical reviews · 2018Review
- Riding the waves of the intercalated disc of the heart.Biophysical reviews · 2018Review
- VASP regulates leukocyte infiltration, polarization, and vascular repair after ischemia.The Journal of cell biology · 2018Article
- Spectrin-based pathways underlying electrical and mechanical dysfunction in cardiac disease.Expert review of cardiovascular therapy · 2018Article
- Transient cardiomyocyte fusion regulates cardiac development in zebrafish.Nature communications · 2017Article
- Ankyrins and Spectrins in Cardiovascular Biology and Disease.Frontiers in physiology · 2017Review
- Vasodilator-Stimulated Phosphoprotein (VASP)-dependent and -independent pathways regulate thrombin-induced activation of Rap1b in platelets.Cell communication and signaling : CCS · 2016Article
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Authors and funding
18 authors at 10 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks.
resultsWe generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired.
conclusionsTogether, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities.
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