Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth in eukaryotic cells. The active mTORC1 promotes cellular anabolic processes including protein, pyrimidine, and lipid biosynthesis, and inhibits catabolic processes such as autophagy. Consistent with its growth-promoting functions, hyper-activation of mTORC1 signaling is one of the important pathomechanisms underlying major human health problems including diabetes, neurodegenerative disorders, and cancer. The mTORC1 receives multiple upstream signals such as an abundance of amino acids and growth factors, thus it regulates a wide range of downstream events relevant to cell growth and proliferation control. The regulation of mTORC1 by amino acids is a fast-evolving field with its detailed mechanisms currently being revealed as the precise picture emerges. In this review, we summarize recent progress with respect to biochemical and biological findings in the regulation of mTORC1 signaling on the lysosomal membrane by amino acids.
Highlights
Life Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1137 East Catherine Street, Ann Arbor, MI 48109, USA
MTORC1 plays a key role in suppressing autophagy, a major cellular catabolic process
We summarized current knowledge and understanding of amino acid-sensing mechanisms that regulate mechanistic target of rapamycin complex 1 (mTORC1), especially on the lysosomal membrane of mammalian cells
Summary
Cells in different species developed diverse strategies to sense extracellular cues and adapt to environmental changes. Recent studies demonstrate that the cellular multiunit protein complex, mechanistic target of rapamycin (mTOR) complex 1, functions as a central regulator of cell growth in response to nutrients and growth factors. The FKBP12–rapamycin complex restricts the accessibility of substrates to the active site of mTOR kinase and weakens the mTOR–Raptor interaction and destabilizes the dimeric structure of mTORC1 [6,15,21]. In response to amino acids, Raptor interacts with the lysosomal Ras-related guanosine 5’-triphosphate (GTP)-binding protein (Rag small GTPase protein complex tethering mTORC1 to the lysosomal membrane, where it encounters another small GTPase, Ras homolog enriched in brain (Rheb) that directly interacts with the mTOR kinase and stimulates the activity of mTORC1 [25,26]. The coordinated spatial regulations of both mTORC1 and the TSC complex establish the machinery for sensing multiple environmental cues to regulate cell growth control
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call