DEPTOR Expression Correlates with Muscle Protein Synthesis

Mammalian target of rapamycin (mTOR) has long been declared a focal point of muscle protein synthesis. mTORC1 (an mTOR complex consisting of mTOR, raptor, PRAS40, and mLST8) has been associated with regulation of protein translation in muscle, altering expression and activity levels of key downstream targets S6K1 and eIF-4E-BP1. mTORC1 has been shown to be affected by various stimuli, including nutritional status, growth factors, and mechanical loading. But in past incidents we have found disconnects in muscle protein synthesis and mTOR signaling, stimulating discussions that mTOR content and activation alone may not be able to fully account for muscle protein synthesis. Gaining popularity as a target for anti-cancer therapies, we became interested in DEPTOR, an endogenous inhibitor of mTORC1. Pharmacological inhibition of DEPTOR in cell culture and mouse studies has displayed increases of anabolic signaling in response to atrophic circumstances. We present two unique catabolic conditions in which we explore DEPTOR expression and muscle protein synthesis and demonstrate the first known data proposing that DEPTOR expression is not only influenced by physiological stimuli, including mechanical loading and insulin sensitivity, but that DEPTOR expression strongly correlates with 24-hr cumulative muscle protein synthesis rates.