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Costameric focal adhesion kinase organises load‐dependent p70S6K signalling in skeletal muscle
Author(s) -
Flueck Martin,
Klossner Stephan,
Li Ruowei,
Ruoss Severin,
Seynnes Olivier,
Erskine Robert M,
Narici Marco V
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.829.14
We hypothesized that sarcolemmal adhesion sites of muscle fibres (costameres) are implicated in the load‐dependent regulation of p70S6K signalling towards protein synthesis. Overexpression of focal adhesion kinase (FAK) in rat soleus muscle upregulated the content of the costamere components, gamma‐ and meta‐ vinculin (+153%), p70S6K protein (+40%), and ribosomal transcripts. The expression of p70S6K (−83%), gamma‐ (−39%) and meta‐vinculin (−49%) was reduced with hindlimb unloading and raised again within 24 hours of reloading (p70S6K: 10‐fold; vinculin: 1.5‐fold) in corresponded to FAK activation by Y397 phosphorylation. Similarly, 24 hours of soleus muscle overload increased the content and activation status of FAK and p70S6K. 1 hour after overload the phosphorylation of p70S6K, AKT and 4E‐BP1 was elevated. At this time‐point the content of activated FAK was reduced but was reestablished with co‐overexpression of FAK and its competitor, FRNK, and co‐related with p70S6K content (r=0.74). Changes in muscle loading to human vastus lateralis muscle by bedrest and resistance training reproduced the regulatory relationships between FAK, FAK‐p397 and meta‐vinculin. The observations indicate that remodelling of costameres by FAK is coupled to the load‐dependent control of protein synthetic capacity in vertebrate muscle.