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, 43 (9), 1267-76

Mechanotransduction and the Regulation of mTORC1 Signaling in Skeletal Muscle


Mechanotransduction and the Regulation of mTORC1 Signaling in Skeletal Muscle

Troy A Hornberger. Int J Biochem Cell Biol.


Mechanical stimuli play a major role in the regulation of skeletal muscle mass, and the maintenance of muscle mass contributes significantly to disease prevention and issues associated with the quality of life. Although the link between mechanical signals and the regulation of muscle mass has been recognized for decades, the mechanisms involved in converting mechanical information into the molecular events that control this process remain poorly defined. Nevertheless, our knowledge of these mechanisms is advancing and recent studies have revealed that signaling through a protein kinase called the mammalian target of rapamycin (mTOR) plays a central role in this event. In this review we will, (1) discuss the evidence which implicates mTOR in the mechanical regulation of skeletal muscle mass, (2) provide an overview of the mechanisms through which signaling by mTOR can be regulated, and (3) summarize our current knowledge of the potential mechanisms involved in the mechanical activation of mTOR signaling.


Figure 1
Figure 1. Chronic Mechanical Loading Induces an Increase in Protein Synthesis
Mouse plantaris muscles were subjected to chronic mechanical loading by surgically ablating the synergist muscles (SA) as previously described (Goodman et al., 2011). For a control condition, mice were subjected to a sham surgery. At 7 days after the surgery, rates of protein synthesis were determined with the in vivo SUrface SEnsing of Translation (SUnSET) method (Goodman et al., 2011). Briefly, mice were given an injection of puromycin 30 minutes before the plantaris muscles were collected. (A-D) Cross-sections from the mid-belly of plantaris muscles subjected to sham or SA conditions were mounted adjacent to one another on a slide, and then subjected to immunohistochemistry for laminin (green) and puromycin (red). (A) Merged image of signals obtained for puromycin and laminin. (B) Grayscale image of the signal obtained for puromycin. Note: the intensity of puromycin signal reflects the rate of protein synthesis (Goodman et al., 2011). (C-D) Higher magnification image of a plantaris muscle subjected to SA reveals the presence of small fibers with very high rates of protein synthesis. The bars in A and B indicate a length of 300μm and the bars in C and D indicate a length of 40μm.
Figure 2
Figure 2. Schematic of the General Mechanisms that Regulate mTORC1 Signaling
Signaling by mTORC1 can be activated by numerous stimuli including growth factors, nutrients and mechanical signals. In this schematic, the components of the mTORC1 complex are shaded in purple and the signaling molecules that stimulate mTORC1 signaling are shaded in green, while molecules that inhibit mTORC1 signaling are shaded in red. Dashed lines represent links in the regulatory pathways that have not been clearly established.
Figure 3
Figure 3
Schematic Overview of the Lipids and Enzymatic Pathways that Regulate [PA] and Potentially mTORC1 Signaling.

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