Focal adhesion kinase controls load‐dependent myofibre differentiation

Abstract

The present report tested the hypothesis that focal adhesion kinase (FAK) is a myocellular transducer of mechanical signals towards downstream control of slow, fatigue‐resistant muscle fibres. This examination was approached in an integrative setting combining somatic transgenesis for myocellular FAK overexpression with transcript profiling, morphometry and myography in two physiological rat models for load‐dependent plasticity of anti‐gravitational soleus muscle. The molecular measures identified FAK‐regulated expressional reprogramming of gene ontologies underlying the oxidative and mechanical specialisation of soleus muscle. FAK‐dependent transcript levels were suppressed with unloading but transient elevated along with muscle weight with reloading. The transcript upregulation of energy and protein metabolism with reloading corresponded to increased tyrosine 397 phosphorylation and the translocation of FAK to the sarcolemma. The load‐dependent modulation of the soleus muscle phenotype by FAK was related to fibre regeneration and became manifest as a shift towards slow contractile characteristics with functional overload. Collectively the findings expose spatially controlled FAK signalling as a key upstream element of the mechano‐dependent muscle differentiation.