Regulation of mTOR by Mechanically-Induced Signal Events

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DESCRIPTION (provided by applicant): It is well established that mechanical stimuli play a central role in the regulation of muscle mass and that maintenance of muscle mass contributes to disease prevention and quality of life; however, the mechanisms involved in converting mechanical signals into the molecular events that control this process are not well understood. For example, recent work has established that a rapamycin-sensitive mechanism (presumably mTOR signaling) is necessary for mechanically-induced growth; yet, the molecular components of this pathway have not been clearly defined. Furthermore, the mechanically-induced signaling events that promote the activation of the rapamycin-sensitive pathway are not known. In an effort to better understand the mechanically-induced rapamycin-sensitive pathway, we propose to use an ex-vivo mechanical stimulator in conjunction with various pharmocological and molecular tools to address the following aims 1) determine the upstream molecules involved in the activation of mechanically-induced rapamycin-sensitive pathway, 2) assess the role of mTOR in the mechanically-induced rapamycin-sensitive pathway and 3) elucidate the mechanically-induced mTOR signaling mechanism(s). This work will help define how mechanical stimuli activate the rapamycin-sensitive pathway and will provide fundamental information for future studies aimed at understanding how mechanical information is converted into the biochemical events that regulate muscle mass.