Fibre-type Specific Concentration of Focal Adhesion Kinase at the Sarcolemma: Influence of Fibre Innervation and Regeneration

In skeletal muscles, focal adhesion complexes (FACs) form part of the costamere, a sarcolemmal protein complex that enables lateral transfer of forces and ensures the stability of the sarcolemma. The present investigation tested whether localisation of a major assembly factor of FACs, focal adhesion kinase (FAK), to the sarcolemma parallels the known modulation of FACs by fibre type (innervation pattern) and fibre regeneration. Immunohistochemical experiments indicated that FAK is preferentially associated with the sarcolemma in a high proportion (>74 %) of the (slow-twitch) type I and (fast-twitch) type IIA fibres in normal rat soleus (N-SOL) muscle and of the type IIA fibres in extensor digitorum longus (N-EDL) muscle. In contrast, a low proportion (<15 %) of fast-twitch type IIB and type I fibres in N-EDL showed sarcolemmal FAK immunoreactivity. Cross-reinnervation of slow-twitch rat SOL muscle with the fast EDL nerve induced slow-to-fast fibre transformation and led to a significant reduction in sarcolemmal FAK immunoreactivity in type I and type IIA fibres. Transplantation of the fast EDL into the slow SOL bed with regeneration and reinnervation of the muscle by the SOL nerve (T-EDL) caused a significant increase in sarcolemmal FAK immunoreactivity in new type I and hybrid I/II fibres and a corresponding reduction in sarcolemmal FAK immunoreactivity in 'normal' IIA and IIB fibres. Conversely, sarcolemmal FAK immunoreactivity in small IIB fibres of T-EDL muscle was increased. Correspondingly, the transplanted and regenerated SOL (reinnervated by the fast EDL nerve) maintained the percentage of FAK-positive sarcolemma in the (regenerated) type I and IIA fibres. Thus, the expression and association of FAK with the sarcolemma are regulated (i) by factors that determine the fibre type and (ii) during fibre regeneration. Our data suggest that the integrity of sarcolemmal FACs is dependent on the fibre type and that FAC turnover is increased during regeneration of muscle fibres.