Mechano-transduction to muscle protein synthesis is modulated by FAK

Klossner, Stephan; Hoppeler, Hans; Durieux, Anne-Cécile; Freyssenet, Damien; Flueck, Martin

doi:10.7600/jspfsm.58.53

Cited by 32 publications

(50 citation statements)

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“…2) and content by 20% after just 10 days of ULLS (de Boer et al 2007b). This fall in FAK activity was accompanied by a 50% decrease in the fractional rate of myofibrillar protein synthesis confirming the role of FAK as an upstream modulator of protein synthesis (Klossner et al 2009). …”

Section: Mechanotransductionmentioning

confidence: 90%

Disuse of the musculo-skeletal system in space and on earth

2010

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Muscle mass and strength are well known to decline in response to actual and simulated microgravity exposure. However, despite the considerable knowledge gained on the physiological changes induced by spaceflight, the mechanisms of muscle atrophy and the effectiveness of in-flight countermeasures still need to be fully elucidated. The present review examines the effects and mechanisms of actual and simulated microgravity on single fibre and whole muscle structural and functional properties, protein metabolism, tendon mechanical properties, neural drive and reflex excitability. The effects of inflight countermeasures are also discussed in the light of recent advances in resistive loading techniques, in combined physical, pharmacological and nutritional interventions as well as in the development of artificial gravity systems. Emphasis has been given to the pioneering work of Pietro Enrico di Prampero in the development of artificial gravity systems and in the progress of knowledge on the limits of human muscular performance in space.

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Section: Mechanotransductionmentioning

confidence: 90%

Disuse of the musculo-skeletal system in space and on earth

2010

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“…The integrin-associated tyrosine kinase, FAK, is a potential key regulator of load-regulated costamere content (14,21,39), and FAK is instrumental for coupling costamere formation with myofibril assembly during muscle fiber growth in culture (7,27,45,48). FAK assists the heterodimerization of integrins and the recruitment of focal adhesion components upon the impact of mechanical stress to integrins (22,55).…”

Section: Klossner S LI R Ruoss S Durieux a Flück Mmentioning

confidence: 99%

“…An increased content of FAK being phosphorylated at autoregulatory tyrosine 397 (FAK-pY397) is understood to serve as readout for the initiation of chemical mechanotransduction (28,32,53). This is highlighted by the increased phosphorylation of FAK at Y397 and auxiliary phosphorylation sites in human and rodent muscle with increased loading and a concomitant drop in tyrosine-phosphorylated FAK content with unloading (8,9,12,21,27,54). In culture, this is a rapid process, with FAK-pY397 content being threefold increased within 2 min of stretch and being decreased within the next 10 min without changes in soluble FAK protein (32).…”

mentioning

confidence: 97%

“…18 and 33). In analogy to focal adhesions of noncontractile cells, costameres are thought to mediate the conversion of physical forces into biochemical signaling, which modulates cell morphology and gene and protein expression (4,13,23,27,30,32,42). In culture, this process of mechanotransduction is initiated within seconds through a conformational change in integrins (26).…”

mentioning

confidence: 98%

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Quantitative changes in focal adhesion kinase and its inhibitor, FRNK, drive load-dependent expression of costamere components

Klossner

Ruoss

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Costameres are mechanosensory sites of focal adhesion in the sarcolemma that reinforce the muscle-fiber composite and provide an anchor for myofibrillogenesis. We hypothesized that elevated content of the integrin-associated regulator of costamere turnover in culture, focal adhesion kinase (FAK), drives changes in costamere component content in antigravity muscle in a load-dependent way in correspondence with altered muscle weight. The content of FAK in soleus muscle being phosphorylated at autoregulatory tyrosine 397 (FAK-pY397) was increased after 20 s of stretch. FAK-pY397 content remained elevated after 24 h of stretch-overload due to upregulated FAK content. Overexpression of FAK in soleus muscle fibers by means of gene electrotransfer increased the β1-integrin (+56%) and meta-vinculin (+88%) content. α7-Integrin (P = 0.46) and γ-vinculin (P = 0.18) content was not altered after FAK overexpression. Co-overexpression of the FAK inhibitor FAK-related nonkinase (FRNK) reduced FAK-pY397 content by 33% and increased the percentage of fast-type fibers that arose in connection with hybrid fibers with gene transfer. Transplantation experiments confirmed the association of FRNK expression with slow-to-fast fiber transformation. Seven days of unloading blunted the elevation of FAK-pY397, β1-integrin, and meta-vinculin content with FAK overexpression, and this was reversed by 1 day of reloading. The results highlight that the expression of components for costameric attachment sites of myofibrils is under load- and fiber type-related control via FAK and its inhibitor FRNK.

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“…96 Another possible mechano-sensitive pathway is that of the muscle attachment, or focal adhesion complexes, which represent macromolecular structures situated in the sarcolemma of muscle fibers, that link the extracellular matrix (ECM) to the cytoplasmic cytoskeleton, and consist of a variety of ECM receptors/ integrins, intracellular cytoskeletal, and signaling molecules. 97 Interactions of ECM proteins with integrin receptors stimulate intracellular signaling pathways important in cell growth and migration in adult skeletal muscle. 98 Activation of integrin receptors appears to be a common feature of muscle remodeling in response to a variety of conditions including EE-T and muscular dystrophy.…”

Section: Signal Transduction Regulating Muscle Protein Metabolism Resmentioning

confidence: 99%