MARP1 regulates passive force by locking titin to the sarcomeric thin filament, a mechanism observed in diaphragm myofibers of mechanically ventilated rats and critically ill patients.
Does MARP1 regulate passive force in stressed muscle by interacting with titin and the thin filament?
MARP1 regulates passive force in stressed muscle by locking titin to the thin filament, a mechanism that may protect the sarcomere from mechanical damage.
Muscle ankyrin repeat protein 1 (MARP1) is frequently up-regulated in stressed muscle, but its effect on skeletal muscle function is poorly understood. Here, we focused on its interaction with the titin-N2A element, found in titin's molecular spring region. We show that MARP1 binds to F-actin, and that this interaction is stronger when MARP1 forms a complex with titin-N2A. Mechanics and super-resolution microscopy revealed that MARP1 "locks" titin-N2A to the sarcomeric thin filament, causing increased extension of titin's elastic PEVK element and, importantly, increased passive force. In support of this mechanism, removal of thin filaments abolished the effect of MARP1 on passive force. The clinical relevance of this mechanism was established in diaphragm myofibers of mechanically ventilated rats and of critically ill patients. Thus, MARP1 regulates passive force by locking titin to the thin filament. We propose that in stressed muscle, this mechanism protects the sarcomere from mechanical damage.
Pijl et al. (Mon,) conducted a other in Stressed muscle / critical illness. Muscle ankyrin repeat protein 1 (MARP1) was evaluated on Passive force regulation and titin-N2A locking to the sarcomeric thin filament. MARP1 regulates passive force by locking titin to the sarcomeric thin filament, a mechanism observed in diaphragm myofibers of mechanically ventilated rats and critically ill patients.
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