LRRC8A is an essential component of a mechanoresponsive ion channel signaling complex that tunes skeletal muscle differentiation, muscle cell size, function and metabolic pathways to regulate adiposity and systemic glycemia.
Building on previous work (Liu et al., 2015), it is shown that depletion or rescue of adult skeletal muscle stem cells is sufficient to induce or attenuate age-associated neuromuscular junction deterioration respectively.
Ablation of canonical TGFβ signaling in muscle stem cells at any age is detrimental, and not beneficial, to effective skeletal muscle regeneration due to the promotion of premature fate commitment at the expense of progenitor amplification.
Skeletal muscle stem cells play important roles in the regeneration of neuromuscular junctions, and so present new targets for therapies to treat neuromuscular decline observed in the context of aging and various neuromuscular diseases.
Elastic forces generated by the giant protein titin define both passive and active tension of skeletal muscle fibers and protect the sarcomeric myosin filaments from severe disruption during contraction.