The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease

C Goul, R Peruzzo, R Zoncu - Nature Reviews Molecular Cell Biology, 2023 - nature.com
Abstract The Ser/Thr kinase mechanistic target of rapamycin (mTOR) is a central regulator of
cellular metabolism. As part of mTOR complex 1 (mTORC1), mTOR integrates signals such …

Structural mechanisms of the mTOR pathway

KY Linde-Garelli, KB Rogala - Current Opinion in Structural Biology, 2023 - Elsevier
The mTOR signaling pathway is essential for regulating cell growth and mammalian
metabolism. The mTOR kinase forms two complexes, mTORC1 and mTORC2, which …

Brain-enriched RagB isoforms regulate the dynamics of mTORC1 activity through GATOR1 inhibition

G Figlia, S Müller, AM Hagenston, S Kleber… - Nature Cell …, 2022 - nature.com
Mechanistic target of rapamycin complex 1 (mTORC1) senses nutrient availability to
appropriately regulate cellular anabolism and catabolism. During nutrient restriction …

mTORC1 activity licenses its own release from the lysosomal surface

A Acharya, C Demetriades - Molecular Cell, 2024 - cell.com
Nutrient signaling converges on mTORC1, which, in turn, orchestrates a physiological
cellular response. A key determinant of mTORC1 activity is its shuttling between the …

Cryo-EM structure of the SEA complex

L Tafur, K Hinterndorfer, C Gabus, C Lamanna… - Nature, 2022 - nature.com
The SEA complex (SEAC) is a growth regulator that acts as a GTPase-activating protein
(GAP) towards Gtr1, a Rag GTPase that relays nutrient status to the Target of Rapamycin …

Growth or death? Control of cell destiny by mTOR and autophagy pathways

MI Khalil, MM Ali, J Holail, M Houssein - Progress in Biophysics and …, 2023 - Elsevier
One of the central regulators of cell growth, proliferation, and metabolism is the mammalian
target of rapamycin, mTOR, which exists in two structurally and functionally different …

mTORC1 restricts TFE3 activity by auto-regulating its presence on lysosomes

S Zwakenberg, D Westland, RM van Es, H Rehmann… - Molecular Cell, 2024 - cell.com
To stimulate cell growth, the protein kinase complex mTORC1 requires intracellular amino
acids for activation. Amino-acid sufficiency is relayed to mTORC1 by Rag GTPases on …

[HTML][HTML] PRMT1 orchestrates with SAMTOR to govern mTORC1 methionine sensing via Arg-methylation of NPRL2

C Jiang, J Liu, S He, W Xu, R Huang, W Pan, X Li… - Cell Metabolism, 2023 - cell.com
Methionine is an essential branch of diverse nutrient inputs that dictate mTORC1 activation.
In the absence of methionine, SAMTOR binds to GATOR1 and inhibits mTORC1 signaling …

Structural basis for FLCN RagC GAP activation in MiT-TFE substrate-selective mTORC1 regulation

RM Jansen, R Peruzzo, SA Fromm, AL Yokom… - Science …, 2022 - science.org
The mechanistic target of rapamycin complex 1 (mTORC1) regulates cell growth and
catabolism in response to nutrients through phosphorylation of key substrates. The tumor …

[HTML][HTML] Amino acid sensing and lysosomal signaling complexes

Z Cui, AMN Joiner, RM Jansen, JH Hurley - Current Opinion in Structural …, 2023 - Elsevier
Amino acid pools in the cell are monitored by dedicated sensors, whose structures are now
coming into view. The lysosomal Rag GTPases are central to this pathway, and the …