Stress-dependent activation of myosin in the heart requires thin filament activation and thick filament mechanosensing.

ABSTRACT: Myosin-based regulation in the heart muscle modulates the number of myosin motors available for interaction with calcium-regulated thin filaments, but the signaling pathways mediating the stronger contraction triggered by stretch between heartbeats or by phosphorylation of the myosin regulatory light chain (RLC) remain unclear. Here, we used RLC probes in demembranated cardiac trabeculae to investigate the molecular structural basis of these regulatory pathways. We show that in relaxed trabeculae at near-physiological temperature and filament lattice spacing, the RLC-lobe orientations are consistent with a subset of myosin motors being folded onto the filament surface in the interacting-heads motif seen in isolated filaments. The folded conformation of myosin is disrupted by cooling relaxe

SUBMITTER: Park-Holohan SJ 

PROVIDER: S-EPMC8072254 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature