TY - JOUR
T1 - Regulating Striated Muscle Contraction
T2 - Through Thick and Thin
AU - Brunello, Elisabetta
AU - Fusi, Luca
N1 - We are grateful to M. Irving and D. Warshaw for helpful comments on the manuscript. E.B. was funded by a British Heart Foundation Intermediate Basic Science Research Fellowship (FS/17/3/32604). L.F. was funded by a Sir Henry Dale Fellowship awarded by the Wellcome Trust and the Royal Society (210464/Z/18/Z).
PY - 2023/11/6
Y1 - 2023/11/6
N2 - Force generation in striated muscle is primarily controlled by structural changes in the actin-containing thin filaments triggered by an increase in intracellular calcium concentration. However, recent studies have elucidated a new class of regulatory mechanisms, based on the myosin-containing thick filament, that control the strength and speed of contraction by modulating the availability of myosin motors for the interaction with actin. This review summarizes the mechanisms of thin and thick filament activation that regulate the contractility of skeletal and cardiac muscle. A novel dual-filament paradigm of muscle regulation is emerging, in which the dynamics of force generation depends on the coordinated activation of thin and thick filaments. We highlight the interfilament signaling pathways based on titin and myosin-binding protein-C that couple thin and thick filament regulatory mechanisms. This dual-filament regulation mediates the length-dependent activation of cardiac muscle that underlies the control of the cardiac output in each heartbeat.
AB - Force generation in striated muscle is primarily controlled by structural changes in the actin-containing thin filaments triggered by an increase in intracellular calcium concentration. However, recent studies have elucidated a new class of regulatory mechanisms, based on the myosin-containing thick filament, that control the strength and speed of contraction by modulating the availability of myosin motors for the interaction with actin. This review summarizes the mechanisms of thin and thick filament activation that regulate the contractility of skeletal and cardiac muscle. A novel dual-filament paradigm of muscle regulation is emerging, in which the dynamics of force generation depends on the coordinated activation of thin and thick filaments. We highlight the interfilament signaling pathways based on titin and myosin-binding protein-C that couple thin and thick filament regulatory mechanisms. This dual-filament regulation mediates the length-dependent activation of cardiac muscle that underlies the control of the cardiac output in each heartbeat.
U2 - 10.1146/annurev-physiol-042222-022728
DO - 10.1146/annurev-physiol-042222-022728
M3 - Review article
SN - 0066-4278
VL - 86
SP - 255
EP - 275
JO - Annual Review of Physiology
JF - Annual Review of Physiology
ER -