ArticleThe Journal of cell biology1999
I-band titin in cardiac muscle is a three-element molecular spring and is critical for maintaining thin filament structure.
Article in The Journal of cell biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 239 citations in OpenAlex.
- Solution NMR study of the titin I-band IgI domain I82 shows unusual conformational dynamics.Journal of biomolecular NMR · 2026Article
- Viscoelasticity of the Heart: An Overview of Viscoelastic Measurements at Different Scales.Annual review of biomedical engineering · 2026Review
- Novel Drug Targets in Diastolic Heart Disease.International journal of molecular sciences · 2025Review
- TTN:c.12478del in proximal I-band of titin represents a common molecular cause of dilated cardiomyopathy in Slovenian patients.Orphanet journal of rare diseases · 2025Article
- Titin's cardiac-specific N2B element is critical to mechanotransduction during volume overload of the heart.Journal of molecular and cellular cardiology · 2024Article
- Structural domain in the Titin N2B-us region binds to FHL2 in a force-activation dependent manner.Nature communications · 2024Article
- Molecular insights into titin's A-band.Journal of muscle research and cell motility · 2023Article
- Titin (TTN): from molecule to modifications, mechanics, and medical significance.Cardiovascular research · 2022Review
- Use of animal models to understand titin physiology and pathology.Journal of cellular and molecular medicine · 2022Review
- Molecular characterization of linker and loop-mediated structural modulation and hinge motion in the C4-C5 domains of cMyBPC.Journal of structural biology · 2022Article
- What Can We Learn from Single Sarcomere and Myofibril Preparations?Frontiers in physiology · 2022Review
- Synchrony of sarcomeric movement regulates left ventricular pump function in the in vivo beating mouse heart.The Journal of general physiology · 2021Article
- Single-Molecule Force Spectroscopy Studies of Missense Titin Mutations That Are Likely Causing Cardiomyopathy.Langmuir : the ACS journal of surfaces and colloids · 2021Article
- The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles.Biophysical reviews · 2021Review
- Cardiac sarcomere mechanics in health and disease.Biophysical reviews · 2021Review
- Titin M-line insertion sequence 7 is required for proper cardiac function in mice.Journal of cell science · 2021Article
- The Sarcomeric Spring Protein Titin: Biophysical Properties, Molecular Mechanisms, and Genetic Mutations Associated with Heart Failure and Cardiomyopathy.Current cardiology reports · 2021Review
- Titin N2A Domain and Its Interactions at the Sarcomere.International journal of molecular sciences · 2021Review
- Mechanisms ofJournal of cardiovascular development and disease · 2021Review
- Calcium-dependent titin-thin filament interactions in muscle: observations and theory.Journal of muscle research and cell motility · 2020Review
34 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 6 institutions in 2 countries.
Funding
Abstract
In cardiac muscle, the giant protein titin exists in different length isoforms expressed in the molecule's I-band region. Both isoforms, termed N2-A and N2-B, comprise stretches of Ig-like modules separated by the PEVK domain. Central I-band titin also contains isoform-specific Ig-motifs and nonmodular sequences, notably a longer insertion in N2-B. We investigated the elastic behavior of the I-band isoforms by using single-myofibril mechanics, immunofluorescence microscopy, and immunoelectron microscopy of rabbit cardiac sarcomeres stained with sequence-assigned antibodies. Moreover, we overexpressed constructs from the N2-B region in chick cardiac cells to search for possible structural properties of this cardiac-specific segment. We found that cardiac titin contains three distinct elastic elements: poly-Ig regions, the PEVK domain, and the N2-B sequence insertion, which extends approximately 60 nm at high physiological stretch. Recruitment of all three elements allows cardiac titin to extend fully reversibly at physiological sarcomere lengths, without the need to unfold Ig domains. Overexpressing the entire N2-B region or its NH(2) terminus in cardiac myocytes greatly disrupted thin filament, but not thick filament structure. Our results strongly suggest that the NH(2)-terminal N2-B domains are necessary to stabilize thin filament integrity. N2-B-titin emerges as a unique region critical for both reversible extensibility and structural maintenance of cardiac myofibrils.
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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.