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J Physiol Volume 584, Number 2, 637-650, October 15, 2007 DOI: 10.1113/jphysiol.2007.141457
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SKELETAL MUSCLE AND EXERCISE

De-phosphorylation of MyoD is linking nerve-evoked activity to fast myosin heavy chain expression in rodent adult skeletal muscle

Merete Ekmark1, Zaheer Ahmad Rana1, Greg Stewart2, D. Grahame Hardie2 and Kristian Gundersen1

1 Department of Molecular Biosciences, University of Oslo, Oslo, Norway
2 Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, UK

Elucidating the molecular pathways linking electrical activity to gene expression is necessary for understanding the effects of exercise on muscle. Fast muscles express higher levels of MyoD and lower levels of myogenin than slow muscles, and we have previously linked myogenin to expression of oxidative enzymes. We here report that in slow muscles, compared with fast, 6 times as much of the MyoD is in an inactive form phosphorylated at T115. In fast muscles, 10 h of slow electrical stimulation had no effect on the total MyoD protein level, but the fraction of phosphorylated MyoD was increased 4-fold. Longer stimulation also decreased the total level of MyoD mRNA and protein, while the level of myogenin protein was increased. Fast patterned stimulation did not have any of these effects. Overexpression of wild type MyoD had variable effects in active slow muscles, but increased expression of fast myosin heavy chain in denervated muscles. In normally active soleus muscles, MyoD mutated at T115 (but not at S200) increased the number of fibres containing fast myosin from 50% to 85% in mice and from 13% to 62% in rats. These data establish de-phosphorylated active MyoD as a link between the pattern of electrical activity and fast fibre type in adult muscles.

(Received 25 July 2007; accepted after revision 29 August 2007; first published online 30 August 2007)
Corresponding author K. Gundersen: Department of Molecular Biosciences, University of Oslo, PO Box 1041, Blindern, N-0316 Oslo, Norway. Email: kgunder{at}imbv.uio.no


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