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Protein kinase D controls voluntary-running-induced skeletal muscle remodelling
- Source :
- Biochemical Journal. 440:327-335
- Publication Year :
- 2011
- Publisher :
- Portland Press Ltd., 2011.
-
Abstract
- Skeletal muscle responds to exercise by activation of signalling pathways that co-ordinate gene expression to sustain muscle performance. MEF2 (myocyte enhancer factor 2)-dependent transcriptional activation of MHC (myosin heavy chain) genes promotes the transformation from fast-twitch into slow-twitch fibres, with MEF2 activity being tightly regulated by interaction with class IIa HDACs (histone deacetylases). PKD (protein kinase D) is known to directly phosphorylate skeletal muscle class IIa HDACs, mediating their nuclear export and thus derepression of MEF2. In the present study, we report the generation of transgenic mice with inducible conditional expression of a dominant-negative PKD1kd (kinase-dead PKD1) protein in skeletal muscle to assess the role of PKD in muscle function. In control mice, long-term voluntary running experiments resulted in a switch from type IIb+IId/x to type IIa plantaris muscle fibres as measured by indirect immunofluorescence of MHCs isoforms. In mice expressing PKD1kd, this fibre type switch was significantly impaired. These mice exhibited altered muscle fibre composition and decreased running performance compared with control mice. Our findings thus indicate that PKD activity is essential for exercise-induced MEF2-dependent skeletal muscle remodelling in vivo.
- Subjects :
- Genetically modified mouse
Mef2
TRPP Cation Channels
Recombinant Fusion Proteins
Green Fluorescent Proteins
Mice, Transgenic
Motor Activity
Biology
Protein Engineering
Biochemistry
Article
Running
Mice
Myosin
medicine
Animals
Humans
Muscle, Skeletal
Molecular Biology
Actin
Enzyme Assays
Myosin Heavy Chains
MEF2 Transcription Factors
Skeletal muscle
Cell Biology
musculoskeletal system
Molecular biology
Actins
Cell biology
Muscle Fibers, Slow-Twitch
medicine.anatomical_structure
Amino Acid Substitution
Myogenic Regulatory Factors
Enzyme Induction
Muscle Fibers, Fast-Twitch
Phosphorylation
Female
Plantaris muscle
Calcium-Calmodulin-Dependent Protein Kinase Type 2
ITGA7
Subjects
Details
- ISSN :
- 14708728 and 02646021
- Volume :
- 440
- Database :
- OpenAIRE
- Journal :
- Biochemical Journal
- Accession number :
- edsair.doi.dedup.....9124cf5e141217c33859a084fc6ffb97