Journal
JOURNAL OF ANATOMY
Volume 223, Issue 5, Pages 525-536Publisher
WILEY
DOI: 10.1111/joa.12101
Keywords
atrophy; focal adhesion kinase; human; hypertrophy; load; muscle; myofibril; vinculin
Categories
Funding
- EU FP7 grant Myoage [223576]
- Medical Research Council [MR/K00414X/1] Funding Source: researchfish
- MRC [MR/K00414X/1] Funding Source: UKRI
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Costameres are mechano-sensory sites of focal adhesion in the sarcolemma that provide a structural anchor for myofibrils. Their turnover is regulated by integrin-associated focal adhesion kinase (FAK). We hypothesized that changes in content of costamere components (beta 1 integrin, FAK, meta-vinculin, gamma-vinculin) with increased and reduced loading of human anti-gravity muscle would: (i) relate to changes in muscle size and molecular parameters of muscle size regulation [p70S6K, myosin heavy chain (MHC)1 and MHCIIA]; (ii) correspond to adjustments in activity and expression of FAK, and its negative regulator, FRNK; and (iii) reflect the temporal response to reduced and increased loading. Unloading induced a progressive decline in thickness of human vastus lateralis muscle after 8 and 34days of bedrest (-4% and -14%, respectively; n=9), contrasting the increase in muscle thickness after 10 and 27days of resistance training (+5% and +13%; n=6). Changes in muscle thickness were correlated with changes in cross-sectional area of type I muscle fibers (r=0.66) and beta 1 integrin content (r=0.76) at the mid-point of altered loading. Changes in meta-vinculin and FAK-pY397 content were correlated (r=0.85) and differed, together with the changes of beta 1 integrin, MHCI, MHCII and p70S6K, between the mid- and end-point of resistance training. By contrast, costamere protein level changes did not differ between time points of bedrest. The findings emphasize the role of FAK-regulated costamere turnover in the load-dependent addition and removal of myofibrils, and argue for two phases of muscle remodeling with resistance training, which do not manifest at the macroscopic level.
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