Structural Biochemistry/Cell Signaling Pathways/Skeletal Muscle Remodeling

Background

Cell signaling pathways are very essential for skeletal muscle remodeling. Skeletal muscles are composed of heterogeneous muscle fibers (myofibers), which are different in their metabolic functions. There are four main types of myofibers: type I, type IIa, type IId/x, and type IIb. Type I and type IIa are specialized in oxidative metabolism, and type IId/x and type IIb are specialized in glycolysis. These skeletal muscles can be remodeled depending on the signaling due mainly to calcium concentrations in the human body and also due to various transcription factors. Muscles can change by transforming the myofibers to consist of more type I or more type IIb depending on how often exercise is done. If a person continually exercises, his/her skeletal muscles will contain more type I myofibers, which increases the overall oxidative metabolism in the body. This in turn keeps the person healthier in multiple ways, mostly in preventing bodily disorders, such as diabetes, muscular dystrophy, etc. These myofibers can be transformed when certain signaling pathways are activated or inhibited.

One of the main component responsible for the transformation of myofibers is the signaling of calcineurin. Calcineurin is a protein phosphatase, which promotes the expression of muscle-specific genes. Calcineurin is activated by myocyte enhancer factor 2 (MEF2), which is a type of transcription factor that will recognize DNA sequences that are rich in adenine-thymine nucleotides. There is also a class II HDAC (histone deacetylase) that controls the activity of MEF2. When the class II HDAC binds to MEF2, MEF2 is inhibited so then it cannot activate the muscle specific genes. To prevent inhibition of MEF2 by HDAC, a HDAC kinase is activated and it phosphorylates the class II HDAC, which gives it a signal/message to leave the nucleus and leave the MEF2 uninhibited.

Exercise

If a person exercises often:

Type IIb --> type IId/x --> type IIa --> type I

If a person doesn’t exercise at all, the myofiber transformation will reverse:

Type I --> type IIa --> type IId/x --> type IIb

Type I myofiber

-maintains a high intracellular calcium concentration (~100-300nM) -for maintaining posture -oxidative metabolism

Type IIb myofiber

-maintains a low calcium concentration (less than 50NM) -fast-twitch muscles -for quick action and strength related -glycolysis

Reference

Bassel-Duby, Rhonda and Olson, Eric N., Signaling Pathways in Skeletal Muscle Remodeling, 2006, http://www.annualreviews.org/doi/full/10.1146/annurev.biochem.75.103004.142622