title: Costamere remodeling with muscle loading and unloading in healthy young men.
abstract: 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 34 days of bedrest (-4% and -14%, respectively; n = 9), contrasting the increase in muscle thickness after 10 and 27 days 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.
authors.affiliation: Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester, UK.
authors.forename: Ruowei
authors.initials: R
authors.lastname: Li
authors.forename: Marco V
authors.initials: MV
authors.lastname: Narici
authors.forename: Robert M
authors.initials: RM
authors.lastname: Erskine
authors.forename: Olivier R
authors.initials: OR
authors.lastname: Seynnes
authors.forename: Jörn
authors.initials: J
authors.lastname: Rittweger
authors.forename: Rado
authors.initials: R
authors.lastname: Pišot
authors.forename: Boštjan
authors.initials: B
authors.lastname: Šimunič
authors.forename: Martin
authors.initials: M
authors.lastname: Flück
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D054974:Costameres / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D052097:Quadriceps Muscle / Q000033:anatomy & histology / Q000502:physiology*; D012146:Rest / Q000502:physiology*; D055815:Young Adult
chemical_list: D003598:Cytoskeletal Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: atrophy; focal adhesion kinase; human; hypertrophy; load; muscle; myofibril; vinculin