Protein kinase D controls voluntary-running-induced skeletal muscle remodelling

• Published in: Biochemical journal Vol. 440; no. 3; p. 327
• Main Authors: Ellwanger, Kornelia, Kienzle, Christine, Lutz, Sylke, Jin, Zheng-Gen, Wiekowski, Maria T, Pfizenmaier, Klaus, Hausser, Angelika
• Format: Journal Article
• Language: English
• Published: England 15.12.2011
• Subjects: Actins - metabolism; Amino Acid Substitution; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; Enzyme Assays; Enzyme Induction; Female; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; MEF2 Transcription Factors; Mice; Mice, Transgenic; Motor Activity; Muscle Fibers, Fast-Twitch - metabolism; Muscle Fibers, Slow-Twitch - metabolism; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiology; Myogenic Regulatory Factors - metabolism; Myosin Heavy Chains - genetics; Myosin Heavy Chains - metabolism; Protein Engineering; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Running; TRPP Cation Channels - genetics; TRPP Cation Channels - metabolism
• ISSN: 1470-8728
• DOI: 10.1042/BJ20101980

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.