ArticleCirculation research2024
Chronic Activation of Tubulin Tyrosination Improves Heart Function.
Article in Circulation research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- The nucleus as a mechanobiological hub in muscle aging.Nucleus (Austin, Tex.) · 2026Review
- Diastolic contributors in cardiomyocytes of a cardiometabolic HFpEF-like mouse model.The Journal of general physiology · 2026Article
- Structure Makes a Difference: IFT Complex in Ciliary Function and Ciliopathy.Cytoskeleton (Hoboken, N.J.) · 2026Review
- Next-generation chemogenetic inhibition using a brain-permeant non-prescription agent.Signal transduction and targeted therapy · 2026Article
- Myocardial Fibrosis in Hypertrophic Cardiomyopathy: Leveraging Quantitative Imaging and Artificial Intelligence for Precision Management.Reviews in cardiovascular medicine · 2026Review
- Mavacamten shows broad benefit in human and mouse models of MYBPC3-related hypertrophic cardiomyopathy.Nature cardiovascular research · 2026Article
- Identification of Centrosome Duplication-Related Biomarkers in Hypertrophic Cardiomyopathy Through Integrative Multi-Omics, Single-Cell Transcriptomics, and Experimental Validation.Journal of the American Heart Association · 2026Article
- JAK1/2 inhibitor ruxolitinib reduces aggregates in cardiac proteinopathy.EMBO molecular medicine · 2026Article
- Article
- Emerging Roles of Tubulin Isoforms and Their Post-Translational Modifications in Microtubule-Based Transport and Cellular Functions.Biomolecules · 2026Review
- The tubulin code in acute ischemic stroke: post-translational reprogramming of the neuronal cytoskeleton and implications for phase-specific neuroprotection.Frontiers in neuroscience · 2026Review
- Tubulin Post-Translational Modifications in Cardiovascular Diseases: Emerging Mechanisms and Therapeutic Modulation by Traditional Chinese Medicine.Drug design, development and therapy · 2026Review
- Microtubule dynamics and post-translational modifications in cardiovascular diseases: mechanisms and therapeutic implications.Frontiers in cardiovascular medicine · 2026Review
- Suppressing microtubule detyrosination augments adeno-associated virus 2 endosomal escape and gene delivery.Journal of cell science · 2025Article
- Systemic administration of analgesic buprenorphine, but not carprofen, affects cardiomyocyte contractility in rodents.Journal of molecular and cellular cardiology plus · 2025Article
- Lower left ventricular ejection time in MYBPC3 variant carriers with overt or subclinical hypertrophic cardiomyopathy.ESC heart failure · 2025Article
- Tubulin tyrosine ligase variant perturbs microtubule tyrosination, causing hypertrophy in patient-specific and CRISPR gene-edited iPSC-cardiomyocytes.JCI insight · 2025Article
- Article
- Dysfunctional cardiomyocyte signalling and heart disease.Current opinion in cell biology · 2025Review
- Cardiac MRI Strain as an Early Indicator of Myocardial Dysfunction in Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2025Article
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19 authors.
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Abstract
backgroundHypertrophic cardiomyopathy (HCM) is the most common cardiac genetic disorder caused by sarcomeric gene variants and associated with left ventricular hypertrophy and diastolic dysfunction. The role of the microtubule network has recently gained interest with the findings that microtubule detyrosination (dTyr-MT) is markedly elevated in heart failure. Acute reduction of dTyr-MT by inhibition of the detyrosinase (VASH [vasohibin]/SVBP [small VASH-binding protein] complex) or activation of the tyrosinase (TTL [tubulin tyrosine ligase]) markedly improved contractility and reduced stiffness in human failing cardiomyocytes and thus posed a new perspective for HCM treatment. In this study, we tested the impact of chronic tubulin tyrosination in an HCM mouse model (
methodsAdeno-associated virus serotype 9-mediated TTL transfer was applied in neonatal wild-type rodents, in 3-week-old knock-in mice, and in HCM human induced pluripotent stem cell-derived cardiomyocytes.
resultsWe show (1) TTL for 6 weeks dose dependently reduced dTyr-MT and improved contractility without affecting cytosolic calcium transients in wild-type cardiomyocytes; (2) TTL for 12 weeks reduced the abundance of dTyr-MT in the myocardium, improved diastolic filling, compliance, cardiac output, and stroke volume in knock-in mice; (3) TTL for 10 days normalized cell area in HCM human induced pluripotent stem cell-derived cardiomyocytes; (4) TTL overexpression activated transcription of tubulins and other cytoskeleton components but did not significantly impact the proteome in knock-in mice; (5) SVBP-deficient EHTs exhibited reduced dTyr-MT levels, higher force, and faster relaxation than TTL-deficient and wild-type EHTs. RNA sequencing and mass spectrometry analysis revealed distinct enrichment of cardiomyocyte components and pathways in SVBP-deficient versus TTL-deficient EHTs.
conclusionsThis study provides the first proof of concept that chronic activation of tubulin tyrosination in HCM mice and in human EHTs improves heart function and holds promise for targeting the nonsarcomeric cytoskeleton in heart disease.
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