ArticleProceedings of the National Academy of Sciences of the United States of America2019
Resolving titin's lifecycle and the spatial organization of protein turnover in mouse cardiomyocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- PITX2C deficiency promotes arrhythmogenic remodelling via oxidative stress in atrial myocytes.Journal of molecular and cellular cardiology plus · 2026Article
- Contractility Drives Cardiomyocyte Maturation and the Response to Nanopatterns.Circulation research · 2026Article
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- Article
- Spatial transcriptomics in the adulteLife · 2025Article
- Germline deletion of Rgs2 and/or Rgs5 in male mice does not exacerbate left ventricular remodeling induced by subchronic isoproterenol infusion.Physiological reports · 2025Article
- Visualizing sarcomere and cellular dynamics in skeletal muscle to improve cell therapies.eLife · 2024Article
- Keeping it fresh: ribosomal protein SA sustains sarcomeric function via localized translation.The Journal of clinical investigation · 2024Article
- Myocardial Infarction Suppresses Protein Synthesis and Causes Decoupling of Transcription and Translation.JACC. Basic to translational science · 2024Article
- Cardiomyocyte external mechanical unloading activates modifications of α-actinin differently from sarcomere-originated unloading.The FEBS journal · 2023Article
- What's past is prologue: FRAP keeps delivering 50 years later.Biophysical journal · 2023Review
- Cardiac splicing as a diagnostic and therapeutic target.Nature reviews. Cardiology · 2023Review
- CAR links hypoxia signaling to improved survival after myocardial infarction.Experimental & molecular medicine · 2023Article
- A single-cell RNA labeling strategy for measuring stress response upon tissue dissociation.Molecular systems biology · 2023Article
- Article
- Circadian regulation of cardiac muscle function and protein degradation.Chronobiology international · 2023Article
- Cardiomyocyte Microtubules: Control of Mechanics, Transport, and Remodeling.Annual review of physiology · 2022Review
- Protein Quality Control at the Sarcomere: Titin Protection and Turnover and Implications for Disease Development.Frontiers in physiology · 2022Review
- Microtubule-based transport is essential to distribute RNA and nascent protein in skeletal muscle.Nature communications · 2021Article
- Striated muscle proteins are regulated both by mechanical deformation and by chemical post-translational modification.Biophysical reviews · 2021Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Cardiac protein homeostasis, sarcomere assembly, and integration of titin as the sarcomeric backbone are tightly regulated to facilitate adaptation and repair. Very little is known on how the >3-MDa titin protein is synthesized, moved, inserted into sarcomeres, detached, and degraded. Here, we generated a bifluorescently labeled knockin mouse to simultaneously visualize both ends of the molecule and follow titin's life cycle in vivo. We find titin mRNA, protein synthesis and degradation compartmentalized toward the Z-disk in adult, but not embryonic cardiomyocytes. Originating at the Z-disk, titin contributes to a soluble protein pool (>15% of total titin) before it is integrated into the sarcomere lattice. Titin integration, disintegration, and reintegration are stochastic and do not proceed sequentially from Z-disk to M-band, as suggested previously. Exchange between soluble and integrated titin depends on titin protein composition and differs between individual cardiomyocytes. Thus, titin dynamics facilitate embryonic vs. adult sarcomere remodeling with implications for cardiac development and disease.
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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.