Abstract
The mammalian target of rapamycin complex 1 (mTORC1) integrates amino acid (AA) availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R) is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca2+ stimulation and extracellular signal–regulated kinases 1 and 2 (ERK1/2) activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln), and glycine (Gly), Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCβ-Ca2+-ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism.
Highlights
The mammalian target of rapamycin is a central metabolic regulator that has been implicated in metabolic diseases and is an important effector of metabolic signaling [1,2]. mTOR forms two distinct structural and functional complexes, namely, mammalian target of rapamycin complex 1 (mTORC1) and mTORC2. mTORC1 promotes cell growth primarily by phosphorylating p70 ribosomal S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1); protein translation is promoted [1,3,4].mTORC1 activity is regulated by nutrients, energy levels, and growth factors [5,6,7,8]
We determined whether T1R1/T1R3 may serve as an amino acids (AA) sensor in C2C12 cells
We examined whether the cell-permeable Ca2+ chelator 1,2-bis (2-aminophenoxy) ethane-N,N,N’,N’-tetraacetic acid (BAPTA)-acetoxymethyl ester (BAPTA-AM) can inhibit AA-induced S6K1 and mTOR phosphorylation in myotubes
Summary
The mammalian target of rapamycin (mTOR) is a central metabolic regulator that has been implicated in metabolic diseases and is an important effector of metabolic signaling [1,2]. mTOR forms two distinct structural and functional complexes, namely, mTORC1 and mTORC2. mTORC1 promotes cell growth primarily by phosphorylating p70 ribosomal S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1); protein translation is promoted [1,3,4]. T1R1/T1R3 is a receptor composed of a heterodimer with taste-specific T1R1 and T1R3 G-protein-coupled receptors; taste receptor type 1 member (T1R) 1/3 can serve as a direct sensor of the fed state and AA availability by promoting intracellular Ca2+ concentration and activating extracellular signal–regulated kinases 1 and 2 (ERK1/2) to regulate mTORC1 and autophagy [11]. Heterologous expression studies have revealed that mouse T1R1/T1R3 (mT1R1/mT1R3) is broadly activated by most L-AAs, including serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln) and glycine (Gly), whereas human T1R1/T1R3 (hT1R1/hT1R3) responds to L-Glu and increases intracellular Ca2+ concentration [13,15]. Our study confirmed that T1R1/T1R3 functions as a methionine sensor to activate mTORC1 in C2C12 myotubes
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