De-phosphorylation of MyoD is Linking Nerve-evoked Activity to Fast Myosin Heavy Chain Expression in Rodent Adult Skeletal Muscle

Overview

Journal J Physiol

Specialty Physiology

Date 2007 Sep 1

PMID 17761773

Citations 35

Authors

Merete Ekmark

Zaheer Ahmad Rana

Greg Stewart

D Grahame Hardie

Kristian Gundersen

Affiliations

Soon will be listed here.

Abstract

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.

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