Structural Biology/Biochemistry Seminar
Tuesday October 25, 2016
11:15 AM | 112 KLB
Mechano-Sensors in Muscle
Skeletal muscle has the remarkable ability to adapt to changes in workload, with multiple inputs (mechanical, chemical, and metabolic) converging into final common pathways for muscle growth and adaptation. During active force generation, such as that stimulated by eccentric muscle contraction (ECC), multiple signals change in parallel, including mechanical deformation, changes in phosphorylation patterns and calcium ion fluxes, and depletion of high-energy substrates. Passive stretch eliminates the contribution of metabolism, yet can still cause both mechanical deformation and signal transduction at the muscle plasma membrane (sarcolemma). The importance of signaling for normal muscle physiology is exemplified in the mouse model for Limb Girdle Muscular Dystrophy (LGMD) 2C, where gene targeting of g-sarcoglycan (g-SG) causes severe pathology, including elevated serum creatine kinase, degeneration/regeneration, and extensive fibrosis, yet there is little mechanical fragility. We, and others, have proposed that the SG complex is a critical part of the mechanical signaling machinery and the absence of this complex alters signaling.
Mechanical signaling occurs within the muscle cell, and relies on sensors for mechanical loading found in the sarcolemma or contractile apparatus. However, the extracellular matrix (ECM) surrounding the muscle can alter the loads imposed on the mechano-sensors, and ultimately affect the responses of muscle. We have begun to examine how differences in ECM can change the mechanical properties of muscle. Thus, the ultimate adaptation of muscle to mechanical work is affected by proteins both inside and out.