De-phosphorylation of MyoD is linking nerve-evoked activity to fast myosin heavy chain expression in rodent adult skeletal muscle.
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.
Ekmark
Merete
M
Department of Molecular Biosciences, University of Oslo, PO Box 1041, Blindern, N-0316 Oslo, Norway.
Rana
Zaheer Ahmad
ZA
Stewart
Greg
G
Hardie
D Grahame
DG
Gundersen
Kristian
K
D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D018274:Electroporation; D005260:Female; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D008297:Male; D051379:Mice; D009121:Muscle Denervation; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism*; D009154:Mutation; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000601:surgery; D013997:Time Factors
D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C503801:Myog protein, mouse; C503803:Myog protein, rat; D018008:Myogenin; D012333:RNA, Messenger; D018995:Myosin Heavy Chains