Titin force in muscle cells alters lattice order, thick and thin filament protein formation
Proceedings of the National Academy of Sciences, 2022•National Acad Sciences
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 …
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 …
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.
National Acad Sciences