Focal adhesion kinase is a load-dependent governor of the slow contractile and oxidative muscle phenotype

Durieux, Anne-Cécile; D'Antona, Giuseppe; Desplanches, Dominique; Freyssenet, Damien; Klossner, Stephan; Bottinelli, Roberto; Flück, Martin (2009). Focal adhesion kinase is a load-dependent governor of the slow contractile and oxidative muscle phenotype. Journal of physiology, 587(Pt 14), pp. 3703-17. Oxford: Wiley-Blackwell 10.1113/jphysiol.2009.171355

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Striated muscle exhibits a pronounced structural-functional plasticity in response to chronic alterations in loading. We assessed the implication of focal adhesion kinase (FAK) signalling in mechano-regulated differentiation of slow-oxidative muscle. Load-dependent consequences of FAK signal modulation were identified using a multi-level approach after electrotransfer of rat soleus muscle with FAK-expression plasmid vs. empty plasmid-transfected contralateral controls. Muscle fibre-targeted over-expression of FAK in anti-gravitational muscle for 9 days up-regulated transcript levels of gene ontologies underpinning mitochondrial metabolism and contraction in the transfected belly portion. Concomitantly, mRNA expression of the major fast-type myosin heavy chain (MHC) isoform, MHC2A, was reduced. The promotion of the slow-oxidative expression programme by FAK was abolished after co-expression of the FAK inhibitor FAK-related non-kinase (FRNK). Elevated protein content of MHC1 (+9%) and proteins of mitochondrial respiration (+165-610%) with FAK overexpression demonstrated the translation of transcript differentiation in targeted muscle fibres towards a slow-oxidative muscle phenotype. Coincidentally MHC2A protein was reduced by 50% due to protection of muscle from de-differentiation with electrotransfer. Fibre cross section in FAK-transfected muscle was elevated by 6%. The FAK-modulated muscle transcriptome was load-dependent and regulated in correspondence to tyrosine 397 phosphorylation of FAK. In the context of overload, the FAK-induced gene expression became manifest at the level of contraction by a slow transformation and the re-establishment of normal muscle force from the lowered levels with transfection. These results highlight the analytic power of a systematic somatic transgene approach by mapping a role of FAK in the dominant mechano-regulation of muscular motor performance via control of gene expression.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy
UniBE Contributor:	Flück, Martin
ISSN:	0022-3751
Publisher:	Wiley-Blackwell
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:11
Last Modified:	05 Dec 2022 14:21
Publisher DOI:	10.1113/jphysiol.2009.171355
PubMed ID:	19470782
Web of Science ID:	000268040500033
URI:	https://boris.unibe.ch/id/eprint/31045 (FactScience: 195438)