ArticleThe Journal of cell biology2014
Human myocytes are protected from titin aggregation-induced stiffening by small heat shock proteins.
Article in The Journal of cell biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 107 citations in OpenAlex.
- Caenorhabditis elegans small heat-shock protein HSP-12.6 has a highly specialized protective function towards muscle thick filaments in vivo.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Article
- Selective titin cleavage disrupts cardiac mechanical homeostasis to drive heart failure and fibrosis.Nature cardiovascular research · 2026Article
- Sex-specific effects of fatiguing exercise on skeletal muscle passive mechanics are preserved in aging.bioRxiv : the preprint server for biology · 2026Article
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- Arrhythmogenic Mechanisms of Novel Biomarkers in Cardiac Electrophysiology.Cardiology research and practice · 2026Review
- Chronic and acute mediators of passive viscoelasticity in human skeletal muscle fibres.Experimental physiology · 2025Article
- Mechanically knocking out titin reveals protein tension loss as a trigger of muscle disease.Nature biomedical engineering · 2025Article
- An overview of insights and updates on TTN mutations in cardiomyopathies.Frontiers in pharmacology · 2025Review
- Fatiguing exercise reduces cellular passive Young's modulus in human vastus lateralis muscle.Experimental physiology · 2024Article
- Protein Kinase D Plays a Crucial Role in Maintaining Cardiac Homeostasis by Regulating Post-Translational Modifications of Myofilament Proteins.International journal of molecular sciences · 2024Article
- Titin: roles in cardiac function and diseases.Frontiers in physiology · 2024Review
- Review
- Heat Shock Proteins: Important Helpers for the Development, Maintenance and Regeneration of Skeletal Muscles.Muscles (Basel, Switzerland) · 2023Review
- The Role of Major Biomarkers of Stress in Atrial Fibrillation: A Literature Review.The Journal of innovations in cardiac rhythm management · 2023Review
- Oxidative stress and inflammation distinctly drive molecular mechanisms of diastolic dysfunction and remodeling in female and male heart failure with preserved ejection fraction rats.Frontiers in cardiovascular medicine · 2023Article
- Titin (TTN): from molecule to modifications, mechanics, and medical significance.Cardiovascular research · 2022Review
- Altered Cellular Protein Quality Control System Modulates Cardiomyocyte Function in Volume Overload-Induced Hypertrophy.Antioxidants (Basel, Switzerland) · 2022Article
- Alpha B-Crystallin in Muscle Disease Prevention: The Role of Physical Activity.Molecules (Basel, Switzerland) · 2022Review
- Protein Quality Control at the Sarcomere: Titin Protection and Turnover and Implications for Disease Development.Frontiers in physiology · 2022Review
- The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles.Biophysical reviews · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In myocytes, small heat shock proteins (sHSPs) are preferentially translocated under stress to the sarcomeres. The functional implications of this translocation are poorly understood. We show here that HSP27 and αB-crystallin associated with immunoglobulin-like (Ig) domain-containing regions, but not the disordered PEVK domain (titin region rich in proline, glutamate, valine, and lysine), of the titin springs. In sarcomeres, sHSP binding to titin was actin filament independent and promoted by factors that increased titin Ig unfolding, including sarcomere stretch and the expression of stiff titin isoforms. Titin spring elements behaved predominantly as monomers in vitro. However, unfolded Ig segments aggregated, preferentially under acidic conditions, and αB-crystallin prevented this aggregation. Disordered regions did not aggregate. Promoting titin Ig unfolding in cardiomyocytes caused elevated stiffness under acidic stress, but HSP27 or αB-crystallin suppressed this stiffening. In diseased human muscle and heart, both sHSPs associated with the titin springs, in contrast to the cytosolic/Z-disk localization seen in healthy muscle/heart. We conclude that aggregation of unfolded titin Ig domains stiffens myocytes and that sHSPs translocate to these domains to prevent this aggregation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.