ARS | Publication request: Rapamycin blocks leucine-induced protein synthesis by suppressing mTORC1 activation in skeletal muscle of neonatal pigs

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: February 18, 2008
Publication Date: April 5, 2008
Citation: Suryawan, A., Jeyapalan, A.S., Orellana, R.A., Nguyen, H.V., Wilson, F.A., Davis, T.A. 2008. Rapamycin blocks leucine-induced protein synthesis by suppressing mTORC1 activiation in skeletal muscle of neonatal pigs [abstract]. Federation of American Societies for Experimental Biology Conference. Minisymposium: Nutrient Sensing Mechanisms, April 5-9, 2008, San Diego, California. Abstract #306.5.

Technical Abstract: Skeletal muscle in the neonate grows at a rapid rate due in part to an enhanced sensitivity to the postprandial rise in amino acids, particularly leucine (Leu). To elucidate the molecular mechanism by which Leu stimulates protein synthesis in neonatal muscle, overnight fasted 7-day-old piglets were treated with rapamycin (an inhibitor of mammalian target of rapamycin complex 1/mTORC1) for 1 h and then infused with Leu for 1 h. Fractional rates of protein synthesis and activation of signaling components lead to mRNA translation were determined. Rapamycin completely blocked Leu-induced muscle protein synthesis. Rapamycin markedly reduced raptor-mTOR association, an indicator of mTORC1 activation. Consequently, phosphorylation of mTOR, S6K1, and 4EBP1, and eIF4E•eIF4G complex abundance were decreased and eIF4E•4EBP1 complex abundance was increased. Rapamycin had no effect on the association of mTOR with rictor, a crucial component for mTORC2 activation. Neither Leu nor rapamycin affected the phosphorylation of AMPK, PKB, or TCS2, signaling components that reside upstream of mTOR. eEF2 phosphorylation was not affected by Leu or rapamycin, although current dogma indicates that eEF2 phosphorylation is mTOR-dependent. Taken together, these in vivo data suggest that Leu stimulates muscle protein synthesis by enhancing mTORC1 activation and its downstream effectors.