title: Thick filament mechano-sensing is a calcium-independent regulatory mechanism in skeletal muscle.
abstract: Recent X-ray diffraction studies on actively contracting fibres from skeletal muscle showed that the number of myosin motors available to interact with actin-containing thin filaments is controlled by the stress in the myosin-containing thick filaments. Those results suggested that thick filament mechano-sensing might constitute a novel regulatory mechanism in striated muscles that acts independently of the well-known thin filament-mediated calcium signalling pathway. Here we test that hypothesis using probes attached to the myosin regulatory light chain in demembranated muscle fibres. We show that both the extent and kinetics of thick filament activation depend on thick filament stress but are independent of intracellular calcium concentration in the physiological range. These results establish direct control of myosin motors by thick filament mechano-sensing as a general regulatory mechanism in skeletal muscle that is independent of the canonical calcium signalling pathway.
authors: Randall Division of Cell and Molecular Biophysics and BHF Centre of Research Excellence, King's College London, London SE1 1UL UK.
authors: L
authors: 0000-0003-3992-0114
authors: L
authors: Fusi
authors: Randall Division of Cell and Molecular Biophysics and BHF Centre of Research Excellence, King's College London, London SE1 1UL UK.
authors: E
authors: 0000-0003-3167-4828
authors: E
authors: Brunello
authors: Randall Division of Cell and Molecular Biophysics and BHF Centre of Research Excellence, King's College London, London SE1 1UL UK.
authors: Z
authors: Z
authors: Yan
authors: Randall Division of Cell and Molecular Biophysics and BHF Centre of Research Excellence, King's College London, London SE1 1UL UK.
authors: M
authors: M
authors: Irving
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling; D007700:Kinetics; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology*; D009218:Myosins / Q000502:physiology; D010766:Phosphorylation; D011312:Pressure; D016658:Psoas Muscles / Q000502:physiology; D011817:Rabbits; D012518:Sarcomeres / Q000502:physiology; D015398:Signal Transduction; D013997:Time Factors; D014961:X-Ray Diffraction
chemical_list: D009218:Myosins; D002118:Calcium