Lysosomal cholesterol activates mTORC1 via an SLC38A9–Niemann-Pick C1 signaling complex

BM Castellano, AM Thelen, O Moldavski, MK Feltes… - Science, 2017 - science.org
The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth
regulator that becomes activated at the lysosome in response to nutrient cues. Here, we …

Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1

HR Shin, YR Citron, L Wang, L Tribouillard, CS Goul… - Science, 2022 - science.org
Lysosomes coordinate cellular metabolism and growth upon sensing of essential nutrients,
including cholesterol. Through bioinformatic analysis of lysosomal proteomes, we identified …

ER–lysosome contacts enable cholesterol sensing by mTORC1 and drive aberrant growth signalling in Niemann–Pick type C

CY Lim, OB Davis, HR Shin, J Zhang, CA Berdan… - Nature cell …, 2019 - nature.com
Cholesterol activates the master growth regulator, mTORC1 kinase, by promoting its
recruitment to the surface of lysosomes by the Rag guanosine triphosphatases (GTPases) …

mTORC1 activity repression by late endosomal phosphatidylinositol 3, 4-bisphosphate

AL Marat, A Wallroth, WT Lo, R Müller, GD Norata… - Science, 2017 - science.org
Nutrient sensing by mechanistic target of rapamycin complex 1 (mTORC1) on lysosomes
and late endosomes (LyLEs) regulates cell growth. Many factors stimulate mTORC1 activity …

Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1

S Wang, ZY Tsun, RL Wolfson, K Shen, GA Wyant… - Science, 2015 - science.org
The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth
regulator that responds to multiple environmental cues. Amino acids stimulate, in a Rag …

Differential regulation of mTORC1 by leucine and glutamine

JL Jewell, YC Kim, RC Russell, FX Yu, HW Park… - Science, 2015 - science.org
The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates
environmental and intracellular signals to regulate cell growth. Amino acids stimulate …

The GATOR–Rag GTPase pathway inhibits mTORC1 activation by lysosome-derived amino acids

GG Hesketh, F Papazotos, J Pawling, D Rajendran… - Science, 2020 - science.org
The mechanistic target of rapamycin complex 1 (mTORC1) couples nutrient sufficiency to
cell growth. mTORC1 is activated by exogenously acquired amino acids sensed through the …

mTORC1 regulates a lysosome-dependent adaptive shift in intracellular lipid species

AM Hosios, ME Wilkinson, MC McNamara… - Nature …, 2022 - nature.com
The mechanistic target of rapamycin complex 1 (mTORC1) senses and relays environmental
signals from growth factors and nutrients to metabolic networks and adaptive cellular …

The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling

PP Hsu, SA Kang, J Rameseder, Y Zhang, KA Ottina… - science, 2011 - science.org
The mammalian target of rapamycin (mTOR) protein kinase is a master growth promoter that
nucleates two complexes, mTORC1 and mTORC2. Despite the diverse processes controlled …

Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis

AM Robitaille, S Christen, M Shimobayashi, M Cornu… - Science, 2013 - science.org
The Ser-Thr kinase mammalian target of rapamycin (mTOR) controls cell growth and
metabolism by stimulating glycolysis and synthesis of proteins and lipids. To further …