Titin force in muscle cells alters lattice order, thick and thin filament protein formation
2022-11-29 | journal article
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Titin force in muscle cells alters lattice order, thick and thin filament protein formation
Hessel, A. L.; Ma, W.; Mazara, N.; Rice, P. E.; Nissen, D.; Gong, H. & Kuehn, M. et al. (2022)
Proceedings of the National Academy of Sciences of the United States of America, 119(48) art. e2209441119. DOI: https://doi.org/10.1073/pnas.2209441119
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Details
- Authors
- Hessel, Anthony L.; Ma, Weikang; Mazara, Nicole; Rice, Paige E.; Nissen, Devin; Gong, Henry; Kuehn, Michel; Irving, Thomas; Linke, Wolfgang A.
- Abstract
- Skeletal muscle force production is increased at longer compared to shorter muscle lengths because of length-dependent priming of thick filament proteins in the contractile unit before contraction. Using small-angle X-ray diffraction in combination with a mouse model that specifically cleaves the stretch-sensitive titin protein, we found that titin cleavage diminished the length-dependent priming of the thick filament. Strikingly, a titin-sensitive, length-dependent priming was also present in thin filaments, which seems only possible via bridge proteins between thick and thin filaments in resting muscle, potentially myosin-binding protein C. We further show that these bridges can be forcibly ruptured via high-speed stretches. Our results advance a paradigm shift to the fundamental regulation of length-dependent priming, with titin as the key driver.
- Issue Date
- 29-November-2022
- Journal
- Proceedings of the National Academy of Sciences of the United States of America
- Project
- SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz
SFB 1002 | A08: Translationale und posttranslationale Kontrolle trunkierter Titinproteine in Kardiomyozyten von Patienten mit dilatativer Kardiomyopathie
SFB 1002 | A08: Translationale und posttranslationale Kontrolle trunkierter Titinproteine in Kardiomyozyten von Patienten mit dilatativer Kardiomyopathie - Working Group
- RG Linke (Kardiovaskuläre Physiologie)
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Language
- English