Nitric-oxide synthase is a mechanical signal transducer that modulates talin and vinculin expression.
Mechanical stimuli can cause changes in muscle mass and structure which indicate that mechanisms exist for transducing mechanical stimuli into signals that influence gene expression. Myotendinous junctions show adaptations to modified muscle loading which suggest that these are transcriptionally distinct domains in muscle fibers that may experience local regulation of expression of structural proteins that are concentrated at these sites. Vinculin and talin are cytoskeletal proteins that are highly enriched at myotendinous junctions that we hypothesize to be subject to local transcriptional regulation. Our findings show that mechanical stimulation of muscle cells in vivo and in vitro causes an increase in the expression of vinculin and talin that is mediated by nitric oxide. Furthermore, nitric oxide-stimulated increases in vinculin and talin expression occur through a protein kinase G-dependent pathway and therefore differ from other mechanisms through which nitric oxide has been shown previously to modulate transcription. Analysis of vinculin mRNA distribution in mechanically stimulated muscle fibers shows that the mRNA is highly concentrated at myotendinous junctions, which supports the hypothesis that myotendinous junctions are distinct domains in which the expression of cytoskeletal proteins is modulated by mechanical stimuli through a nitric oxide and protein kinase G-dependent pathway.
Tidball
J G
JG
Department of Physiological Science, University of California, Los Angeles, California 90095-1527, USA. jtidball@physci.ucla.edu
Spencer
M J
MJ
Wehling
M
M
Lavergne
E
E
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles; D002460:Cell Line; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D007211:Indoles; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016608:Talin / Q000235:genetics* / Q000378:metabolism; D016596:Vinculin / Q000235:genetics* / Q000378:metabolism
D000470:Alkaloids; D002227:Carbazoles; D007211:Indoles; D009124:Muscle Proteins; D012333:RNA, Messenger; C110881:S-nitro-N-acetylpenicillamine; D016608:Talin; D016596:Vinculin; C073601:KT 5823; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017869:Cyclic GMP-Dependent Protein Kinases; D010396:Penicillamine