Amino Acid-Dependent mTORC1 Regulation by the Lysosomal Membrane Protein SLC38A9

Jung, Jennifer; Genau, Heide Marika; Behrends, Christian

doi:10.1128/mcb.00125-15

Cited by 266PI3K/AKT/mTOR signaling in cancerAutophagy in Disease and TherapyMetabolism, Diabetes, and Cancer

Amino Acid-Dependent mTORC1 Regulation by the Lysosomal Membrane Protein SLC38A9

Open access

Jung, Jennifer, Genau, Heide Marika, Behrends, Christian·2015·Molecular and Cellular Biology

DOI 10.1128/mcb.00125-15PMC PMC4475919

Open this paper in CoChat — free account Open PDF

Abstract

The serine/threonine kinase mTORC1 regulates cellular homeostasis in response to many cues, such as nutrient status and energy level. Amino acids induce mTORC1 activation on lysosomes via the small Rag GTPases and the Ragulator complex, thereby controlling protein translation and cell growth. Here, we identify the human 11-pass transmembrane protein SLC38A9 as a novel component of the Rag-Ragulator complex. SLC38A9 localizes with Rag-Ragulator complex components on lysosomes and associates with Rag GTPases in an amino acid-sensitive and nucleotide binding state-dependent manner. Depletion of SLC38A9 inhibits mTORC1 activity in the presence of amino acids and in response to amino acid replenishment following starvation. Conversely, SLC38A9 overexpression causes RHEB (Ras homolog enriched in brain) GTPase-dependent hyperactivation of mTORC1 and partly sustains mTORC1 activity upon amino acid deprivation. Intriguingly, during amino acid starvation mTOR is retained at the lysosome upon SLC38A9 depletion but fails to be activated. Together, the findings of our study reveal SLC38A9 as a Rag-Ragulator complex member transducing amino acid availability to mTORC1 activity.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1128/mcb.00125-15

Cites

55 of 56 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Presence of amino acids, arginine in particular, are transmitted through SLC38A9-v-ATPase to the Rag GTPases.
“Studies of SLC38A9 suggest that presence of amino acids, arginine in particular (Wang et al., 2015) are transmitted through SLC38A9-v-ATPase to the Rag GTPases (Jung et al., 2015; Rebsamen et al., 2015; Wang et al., 2015).”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Jung et al., 2015

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Predicting transmembrane protein topology with a hidden markov model: application to complete genomes11Edited by F. Cohen
Krogh, A., Larsson, B., von Heijne, G., & Sonnhammer, E. L. L. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.4315 · Cited by 12,654 · see citing works
Antimicrobial Autophagy: A Conserved Innate Immune Response in Drosophila
Moy, R. H., & Cherry, S. R. (2013) · Journal of Innate Immunity · doi:10.1159/000350326 · Cited by 3,549 · see citing works
mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery.
Kim, D.-H., Sarbassov, D., Ali, S. M., King, J. E., Latek, R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 3,135 · see citing works
Defining the role of mTOR in cancer
Guertin, D. A., & Sabatini, D. M. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.05.008 · Cited by 2,833 · see citing works
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773 · see citing works
Ragulator-Rag Complex Targets mTORC1 to the Lysosomal Surface and Is Necessary for Its Activation by Amino Acids
Sancak, Y., Bar-Peled, L., Zoncu, R., Markhard, A. L., Nada, S., & Sabatini, D. M. (2010) · Cell · doi:10.1016/j.cell.2010.02.024 · Cited by 2,464 · see citing works
Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
Inoki, K., Li, Y., Xu, T., & Guan, K.-L. (2003) · Genes & Development · doi:10.1101/gad.1110003 · Cited by 1,911 · see citing works
Bidirectional Transport of Amino Acids Regulates mTOR and Autophagy
Nicklin, P., Bergman, P., Zhang, B., Triantafellow, E., Wang, H., Nyfeler, B., Yang, H., Hild, M., Kung, C., Wilson, C., et al. (2009) · Cell · doi:10.1016/j.cell.2008.11.044 · Cited by 1,798 · see citing works
A tissue-specific atlas of mouse protein phosphorylation and expression
Huttlin, E. L., Jedrychowski, M. P., Elias, J. E., Goswami, T., Rad, R., Beausoleil, S. A., Villén, J., Haas, W., Sowa, M. E., & Gygi, S. P. (2010) · Cell · doi:10.1016/j.cell.2010.12.001 · Cited by 1,778 · see citing works
Drug—target network
Yıldırım, M. A., Goh, K.-I., Cusick, M. E., Barabási, A.-Ĺ., & Vidal, M. (2007) · Nature Biotechnology · doi:10.1038/nbt1338 · Cited by 1,711 · see citing works
mTORC1 Senses Lysosomal Amino Acids Through an Inside-Out Mechanism That Requires the Vacuolar H <sup>+</sup> -ATPase
Zoncu, R., Bar-Peled, L., Efeyan, A., Wang, S., Sancak, Y., & Sabatini, D. M. (2011) · Science · doi:10.1126/science.1207056 · Cited by 1,673 · see citing works
Network organization of the human autophagy system
Behrends, C., Sowa, M. E., Gygi, S. P., & Harper, J. W. (2010) · Nature · doi:10.1038/nature09204 · Cited by 1,554 · see citing works
Self-citation
Defining the Human Deubiquitinating Enzyme Interaction Landscape
Sowa, M. E., Bennett, E. J., Gygi, S. P., & Harper, J. W. (2009) · Cell · doi:10.1016/j.cell.2009.04.042 · Cited by 1,512 · see citing works
Amino Acid Sufficiency and mTOR Regulate p70 S6 Kinase and eIF-4E BP1 through a Common Effector Mechanism
Hara, K., Yonezawa, K., Weng, Q.-P., Kozlowski, M. T., BELHAM, C. M., & Avruch, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.23.14484 · Cited by 1,370 · see citing works
Regulation of the mTOR Complex 1 Pathway by Nutrients, Growth Factors, and Stress
Sengupta, S., Peterson, T. R., & Sabatini, D. M. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.026 · Cited by 1,234 · see citing works
Tuberous Sclerosis Complex Gene Products, Tuberin and Hamartin, Control mTOR Signaling by Acting as a GTPase-Activating Protein Complex toward Rheb
Tee, A. R., Manning, B. D., Roux, P. P., Cantley, L. C., & Blenis, J. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00506-2 · Cited by 1,211 · see citing works
A Tumor Suppressor Complex with GAP Activity for the Rag GTPases That Signal Amino Acid Sufficiency to mTORC1
Bar-Peled, L., Chantranupong, L., Cherniack, A. D., Chen, W. W., Ottina, K. A., Grabiner, B. C., Spear, E. D., Carter, S. L., Meyerson, M., & Sabatini, D. M. (2013) · Science · doi:10.1126/science.1232044 · Cited by 1,080 · cited 4× · see citing works
“While the GATOR1 (GAP activity toward Rags) complex exhibits GAP activity toward RagA/B (21), FLCN (folliculin) and its interacting partners, FNIP1 (folliculin-interacting protein 1) and FNIP2, act on RagC/D (20).”
BackgroundInfluential
Rheb Binds and Regulates the mTOR Kinase
Long, X., Lin, Y., Ortiz-Vega, S., Yonezawa, K., & Avruch, J. (2005) · Current Biology · doi:10.1016/j.cub.2005.02.053 · Cited by 1,005 · see citing works
GβL, a Positive Regulator of the Rapamycin-Sensitive Pathway Required for the Nutrient-Sensitive Interaction between Raptor and mTOR
Kim, D., Sarbassov, D. D., Ali, S. M., Latek, R. R., Guntur, K., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00114-x · Cited by 955 · see citing works
Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1
Bar-Peled, L., Schweitzer, L. D., Zoncu, R., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.07.032 · Cited by 918 · cited 14× · see citing works
“Cycling of mTOR between cytosol and lysosome generally is coupled to its inactive and active states, respectively, and depends on Rag GTPases, Ragulator, TSC, and RHEB GTPase (9, 16, 23, 31).”
BackgroundInfluential
Lysosomal positioning coordinates cellular nutrient responses
Korolchuk, V. I., Saiki, S., Lichtenberg, M., Siddiqi, F. H., Roberts, E. A., Imarisio, S., Jahreiss, L., Sarkar, S., Futter, M., Menzies, F. M., et al. (2011) · Nature Cell Biology · doi:10.1038/ncb2204 · Cited by 891 · see citing works
Leucyl-tRNA Synthetase Is an Intracellular Leucine Sensor for the mTORC1-Signaling Pathway
Han, J. M., Jeong, S. J., Park, M. C., Kim, G., Kwon, N. H., Kim, H. K., Ha, S. H., Ryu, S. H., & Kim, S. (2012) · Cell · doi:10.1016/j.cell.2012.02.044 · Cited by 824 · see citing works
The amino acid transporter SLC38A9 is a key component of a lysosomal membrane complex that signals arginine sufficiency to mTORC1
Wang, S., Tsun, Z., Wolfson, R. L., Shen, K., Wyant, G., Plovanich, M. E., Yuan, E. D., Jones, T. D., Chantranupong, L., Comb, W. C., et al. (2015) · Science · doi:10.1126/science.1257132 · Cited by 772 · see citing works
SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1
Rebsamen, M., Pochini, L., Stasyk, T., de Araújo, M. E. G., Galluccio, M., Kandasamy, R. K., Snijder, B., Fauster, A., Rudashevskaya, E. L., Bruckner, M., et al. (2015) · Nature · doi:10.1038/nature14107 · Cited by 673 · see citing works
TBC1D7 Is a Third Subunit of the TSC1-TSC2 Complex Upstream of mTORC1
Dibble, C. C., Elis, W., Menon, S., Qin, W., Klekota, J., Asara, J. M., Finan, P. M., Kwiatkowski, D. J., Murphy, L. O., & Manning, B. D. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.06.009 · Cited by 612 · see citing works
The Folliculin Tumor Suppressor Is a GAP for the RagC/D GTPases That Signal Amino Acid Levels to mTORC1
Tsun, Z.-Y., Bar-Peled, L., Chantranupong, L., Zoncu, R., Wang, T., Kim, C., Spooner, E., & Sabatini, D. M. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.09.016 · Cited by 565 · see citing works
Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2
Demetriades, C., Doumpas, N., & Teleman, A. A. (2014) · Cell · doi:10.1016/j.cell.2014.01.024 · Cited by 412 · see citing works
Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH
Heuser, J. (1989) · The Journal of cell biology · doi:10.1083/jcb.108.3.855 · Cited by 390 · see citing works
Rheb Binds Tuberous Sclerosis Complex 2 (TSC2) and Promotes S6 Kinase Activation in a Rapamycin- and Farnesylation-dependent Manner
Castro, A. F., Rebhun, J. F., Clark, G. J., & Quilliam, L. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c300226200 · Cited by 381 · see citing works
The Tuberous Sclerosis Protein TSC2 Is Not Required for the Regulation of the Mammalian Target of Rapamycin by Amino Acids and Certain Cellular Stresses
Smith, E. M., FINN, S. G., Tee, A. R., Browne, G. J., & Proud, C. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414499200 · Cited by 354 · see citing works
Amino acid availability regulates p70 S6 kinase and multiple translation factors
Wang, X., Campbell, L., Miller, C. M., & Proud, C. G. (1998) · Biochemical Journal · doi:10.1042/bj3340261 · Cited by 338 · see citing works
Molecular Analysis of System N Suggests Novel Physiological Roles in Nitrogen Metabolism and Synaptic Transmission
Chaudhry, F. A., Reimer, R. J., Križaj, D., Barber, D. L., Storm‐Mathisen, J., Copenhagen, D. R., & Edwards, R. H. (1999) · Cell · doi:10.1016/s0092-8674(00)81674-8 · Cited by 331 · see citing works
Regulation of targets of mTOR (mammalian target of rapamycin) signalling by intracellular amino acid availability
BEUGNET, A., TEE, A. R., TAYLOR, P. M., & PROUD, C. G. (2003) · Biochemical Journal · doi:10.1042/bj20021266 · Cited by 307 · see citing works
Cloning and Functional Identification of a Neuronal Glutamine Transporter
Varoqui, H., Yao, D., Zhu, H., Hong, M., & Erickson, J. D. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.6.4049 · Cited by 301 · see citing works
Cloning of an Amino Acid Transporter with Functional Characteristics and Tissue Expression Pattern Identical to That of System A
Sugawara, M., Nakanishi, T., Fei, Y.-J., Huang, W. Y., Ganapathy, M. E., Leibach, F. H., & Ganapathy, V. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000205200 · Cited by 254 · see citing works
Novel G Proteins, Rag C and Rag D, Interact with GTP-binding Proteins, Rag A and Rag B*
Sekiguchi, T., Hirose, E., Nakashima, N., Ii, M., & Nishimoto, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m004389200 · Cited by 249 · see citing works
A Novel System A Isoform Mediating Na+/Neutral Amino Acid Cotransport
Yao, D., Mackenzie, B., Hong, M., Varoqui, H., Zhu, H., Hediger, M. A., & Erickson, J. D. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002965200 · Cited by 242 · see citing works
Identification and characterization of a lysosomal transporter for small neutral amino acids
Sagné, C., Agulhon, C., Ravassard, P., Darmon, M. C., Hamon, M., Mestikawy, S. E., Gasnier, B., & Bruno Giros, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121183498 · Cited by 233 · see citing works
Localization of Rheb to the endomembrane is critical for its signaling function
Buerger, C., DeVries, B., & Stambolic, V. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.03.220 · Cited by 192 · see citing works
Evolutionary origin of amino acid transporter families SLC32, SLC36 and SLC38 and physiological, pathological and therapeutic aspects
Schiöth, H. B., Roshanbin, S., Hägglund, M. G. A., & Fredriksson, R. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.07.012 · Cited by 150 · see citing works
Proton-Assisted Amino Acid Transporter PAT1 Complexes with Rag GTPases and Activates TORC1 on Late Endosomal and Lysosomal Membranes
Ogmundsdottir, M. H., Heublein, S., Kazi, S., Reynolds, B., Visvalingam, S. M., Shaw, M. K., & Goberdhan, D. C. I. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036616 · Cited by 139 · see citing works
Structure and function of ATA3, a new subtype of amino acid transport system A, primarily expressed in the liver and skeletal muscle
Sugawara, M., Nakanishi, T., Fei, Y.-J., Martindale, R. G., Ganapathy, M. E., Leibach, F. H., & Ganapathy, V. (2000) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(00)00349-7 · Cited by 136 · see citing works
Novel Role of the Small GTPase Rheb: Its Implication in Endocytic Pathway Independent of the Activation of Mammalian Target of Rapamycin
Saito, K. (2005) · The Journal of Biochemistry · doi:10.1093/jb/mvi046 · Cited by 128 · see citing works
Activation and Function of the mTORC1 Pathway in Mast Cells
Kim, M., Kuehn, H. S., Metcalfe, D. D., & Gilfillan, A. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.7.4586 · Cited by 121 · see citing works
Identification of SLC38A7 (SNAT7) Protein as a Glutamine Transporter Expressed in Neurons
Hägglund, M. G. A., Sreedharan, S., Nilsson, V. C., Shaik, J. H. A., Almkvist, I., Bäcklin, S., Wränge, Ö., & Fredriksson, R. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.162404 · Cited by 121 · see citing works
Evidence for the transport of neutral as well as cationic amino acids by ATA3, a novel and liver-specific subtype of amino acid transport system A
Hatanaka, T., Huang, W. Y., Ling, R., Prasad, P. D., Sugawara, M., Leibach, F. H., & Ganapathy, V. (2001) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(00)00390-4 · Cited by 118 · see citing works
Cloning of a Novel Family of Mammalian GTP-binding Proteins (RagA, RagBs, RagB1) with Remote Similarity to the Ras-related GTPases
Schürmann, A., Brauers, A., Maßmann, S., Becker, W. B., & Joost, H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.48.28982 · Cited by 118 · see citing works
Cloning and functional characterization of a new subtype of the amino acid transport system N
Nakanishi, T., Kekuda, R., Fei, Y.-J., Hatanaka, T., Sugawara, M., Martindale, R. G., Leibach, F. H., Prasad, P. D., & Ganapathy, V. (2001) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2001.281.6.c1757 · Cited by 117 · see citing works
Rheb and Rags come together at the lysosome to activate mTORC1
Groenewoud, M. J., & Zwartkruis, F. J. T. (2013) · Biochemical Society Transactions · doi:10.1042/bst20130037 · Cited by 96 · see citing works
SNAT2 transceptor signalling via mTOR A role in cell growth and proliferation
Hundal, H. S. (2011) · Frontiers in Bioscience-Elite · doi:10.2741/e332 · Cited by 91 · see citing works
mTOR direct interactions with Rheb-GTPase and raptor: sub-cellular localization using fluorescence lifetime imaging
Yadav, R. B., Burgos, P., Parker, A. W., Iadevaia, V., Proud, C. G., Allen, R. A., O’Connell, J. P., Jeshtadi, A., Stubbs, C. D., & Botchway, S. W. (2013) · BMC Cell Biology · doi:10.1186/1471-2121-14-3 · Cited by 71 · see citing works
Lysosomal amino acid transporter LYAAT‐1 in the rat central nervous system: An in situ hybridization and immunohistochemical study
Agulhon, C., Rostaing, P., Ravassard, P., Sagné, C., Triller, A., & Bruno Giros, A. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10712 · Cited by 38 · see citing works
Amino acid derivatives are substrates or non-transported inhibitors of the amino acid transporter PAT2 (slc36a2)
Edwards, N., Anderson, C. M. H., Gatfield, K. M., Jevons, M., Ganapathy, V., & Thwaites, D. T. (2010) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2010.07.032 · Cited by 30 · see citing works
Influence of Cycloheximide on the Synthesis and Utilization of Amino Acids in Suspension Cultures
Fletcher, J. S., & Beevers, H. (1971) · PLANT PHYSIOLOGY · doi:10.1104/pp.48.3.261 · Cited by 25 · see citing works
Action of cycloheximide on amino acid metabolism in Saccharomyces elipsoideus
Widuczynski, I., & Stoppani, A. O. M. (1965) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(65)90347-8 · Cited by 21 · see citing works
SNAT2 transceptor signalling via mTOR: A role in cell growth and proliferation?
Pinilla, J. (2009) · Frontiers in Bioscience-Elite · doi:10.2741/332 · Cited by 9 · see citing works

Flagged first, then by citations

Sorted by citations

mTOR Signaling in Growth, Metabolism, and Disease
Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.02.004 · Cited by 7,555 · see citing works
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894 · see citing works
From Krebs to clinic: glutamine metabolism to cancer therapy
Altman, B. J., Stine, Z. E., & Dang, C. V. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.71 · Cited by 2,119 · see citing works
mTOR as a central hub of nutrient signalling and cell growth
Kim, J., & Guan, K. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0205-1 · Cited by 1,067 · see citing works
Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease
Panwar, V., Singh, A., Bhatt, M., Tonk, R. K., Azizov, S., Raza, A. S., Sengupta, S., Kumar, D., & Garg, M. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01608-z · Cited by 967 · see citing works
The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway
Chantranupong, L., Scaria, S. M., Saxton, R. A., Gygi, M. P., Shen, K., Wyant, G. A., Wang, T., Harper, J. W., Gygi, S. P., & Sabatini, D. M. (2016) · Cell · doi:10.1016/j.cell.2016.02.035 · Cited by 843 · see citing works
Regulation and metabolic functions of mTORC1 and mTORC2.
Szwed, A., Kim, E., & Jacinto, E. (2021) · Physiological Reviews · doi:10.1152/physrev.00026.2020 · Cited by 723 · see citing works
AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control
González, A., Hall, M. N., Lin, S.-C., & Hardie, D. G. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.01.015 · Cited by 797 · see citing works
Nutrient sensing and TOR signaling in yeast and mammals
González, A., & Hall, M. (2017) · EMBO Journal · doi:10.15252/embj.201696010 · Cited by 684 · see citing works
Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes
Abu-Remaileh, M., Wyant, G. A., Kim, C., Laqtom, N. N., Abbasi, M., Chan, S. H., Freinkman, E., & Sabatini, D. M. (2017) · Science · doi:10.1126/science.aan6298 · Cited by 665 · see citing works
The Lysosome as a Regulatory Hub
Perera, R. M., & Zoncu, R. (2016) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-111315-125125 · Cited by 664 · see citing works
mTORC1 as the main gateway to autophagy
Rabanal-Ruiz, Y., Otten, E. G., & Korolchuk, V. (2017) · Essays in Biochemistry · doi:10.1042/ebc20170027 · Cited by 505 · see citing works
SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway
Gu, X., Orozco, J. M., Saxton, R., Condon, K. J., Liu, G. Y., Krawczyk, P. A., Scaria, S. M., Harper, J. W., Gygi, S., & Sabatini, D. (2017) · Science · doi:10.1126/science.aao3265 · Cited by 533 · see citing works
The dawn of the age of amino acid sensors for the mTORC1 pathway
Wolfson, R. L., & Sabatini, D. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.07.001 · Cited by 500 · see citing works
The mechanistic target of rapamycin: the grand conducTOR of metabolism and aging
Kennedy, B. K., & Lamming, D. W. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.009 · Cited by 544 · see citing works
Amino acid homeostasis and signalling in mammalian cells and organisms
Bröer, S., & Bröer, A. (2017) · Biochemical Journal · doi:10.1042/bcj20160822 · Cited by 496 · see citing works
Autophagy in the liver: functions in health and disease
Ueno, T., & Komatsu, M. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.185 · Cited by 500 · see citing works
New Insights Into the Role of mTOR Signaling in the Cardiovascular System
Sciarretta, S., Forte, M., Frati, G., & Sadoshima, J. (2018) · Circulation Research · doi:10.1161/circresaha.117.311147 · Cited by 489 · see citing works
mTORC1 activator SLC38A9 is required to efflux essential amino acids from lysosomes and use protein as a nutrient
Wyant, G., Abu-Remaileh, M., Wolfson, R. L., Chen, W. W., Freinkman, E., Danai, L. V., Heiden, M. V. V., & Sabatini, D. (2017) · Cell · doi:10.1016/j.cell.2017.09.046 · Cited by 434 · see citing works
mTOR as a central regulator of lifespan and aging
Papadopoli, D. J., Boulay, K., Kazak, L., Pollak, M., Mallette, F. A., Topisirović, I., & Hulea, L. (2019) · F1000Research · doi:10.12688/f1000research.17196.1 · Cited by 431 · see citing works
Metabolism of Amino Acids in Cancer
Wei, Z. C., Liu, X., Cheng, C., Yu, W., & Yi, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.603837 · Cited by 439 · see citing works
Mechanisms of autophagy–lysosome dysfunction in neurodegenerative diseases
Nixon, R. A., & Rubinsztein, D. C. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00757-5 · Cited by 435 · see citing works
Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy
Yang, L., Chu, Z., Liu, M., Zou, Q., Li, J., Liu, Q., Wang, Y., Wang, T., Xiang, J., & Wang, B. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01453-1 · Cited by 362 · see citing works
Nutrient regulation of mTORC1 at a glance
Condon, K. J., & Sabatini, D. (2019) · Journal of Cell Science · doi:10.1242/jcs.222570 · Cited by 288 · see citing works
ER-lysosome contacts enable cholesterol sensing by mTORC1 and drive aberrant growth signaling in Niemann-Pick type C
Lim, C.-Y., Davis, O. B., Shin, H. R., Zhang, J., Berdan, C. A., Jiang, X.-T., Counihan, J. L., Ory, D., Nomura, D., & Zoncu, R. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0391-5 · Cited by 283 · see citing works
Amino acid-dependent control of mTORC1 signaling: a variety of regulatory modes
Takahara, T., Amemiya, Y., Sugiyama, R., Maki, M., & Shibata, H. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-020-00679-2 · Cited by 300 · see citing works
The lysosome as a command-and-control center for cellular metabolism
Lim, C.-Y., & Zoncu, R. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201607005 · Cited by 274 · see citing works
Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology
Settembre, C., & Perera, R. M. (2023) · Nature reviews. Molecular cell biology · doi:10.1038/s41580-023-00676-x · Cited by 269 · see citing works
Galectins Control mTOR in Response to Endomembrane Damage
Jia, J., Abudu, Y. P., Claude‐Taupin, A., Gu, Y., Kumar, S. G., Choi, S. W., Peters, R. S., Mudd, M. H., Allers, L., Salemi, M., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.03.009 · Cited by 288 · see citing works
GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2Preprint
Ye, J., Palm, W., Peng, M., King, B., Lindsten, T., Li, M. O., Koumenis, C., & Thompson, C. B. (2015) · Genes & Development · doi:10.1101/gad.269324.115 · Cited by 289 · see citing works
Watch What You (Self-) Eat: Autophagic Mechanisms that Modulate Metabolism
Lahiri, V., Hawkins, W. D., & Klionsky, D. J. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.03.003 · Cited by 286 · see citing works
The molecular basis of nutrient sensing and signalling by mTORC1 in metabolism regulation and disease
Goul, C., Peruzzo, R., & Zoncu, R. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00641-8 · Cited by 269 · see citing works
Emerging Roles for the Lysosome in Lipid Metabolism
Thelen, A. M., & Zoncu, R. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.07.006 · Cited by 268 · see citing works
Amino Acid Sensing by mTORC1: Intracellular Transporters Mark the Spot
Goberdhan, D., Wilson, C., & Harris, A. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.03.013 · Cited by 240 · see citing works
The crucial impact of lysosomes in aging and longevity
Carmona‐Gutiérrez, D., Hughes, A. L., Madeo, F., & Ruckenstuhl, C. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.009 · Cited by 244 · see citing works
Glutamine and asparagine activate mTORC1 independently of Rag GTPases
Meng, D.-L., Yang, Q., Wang, H., Melick, C. H., Navlani, R., Frank, A., & Jewell, J. L. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ac119.011578 · Cited by 192 · see citing works
Multiple amino acid sensing inputs to mTORC1
Shimobayashi, M., & Hall, M. (2015) · Cell Research · doi:10.1038/cr.2015.146 · Cited by 216 · see citing works
mTORC1 as a Regulator of Mitochondrial Functions and a Therapeutic Target in Cancer
de la Cruz-López, K. G., Toledo-Guzmán, M. E., Sánchez, E. O., & Carrancá, A. G. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01373 · Cited by 215 · see citing works
The lysosome: a crucial hub for AMPK and mTORC1 signalling.
Carroll, B., & Dunlop, E. (2017) · Biochemical Journal · doi:10.1042/bcj20160780 · Cited by 173 · see citing works
TOR Complexes and the Maintenance of Cellular Homeostasis.
Eltschinger, S., & Loewith, R. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.10.003 · Cited by 181 · see citing works
mTOR signaling in stem and progenitor cells
Meng, D.-L., Frank, A., & Jewell, J. L. (2018) · Development · doi:10.1242/dev.152595 · Cited by 176 · see citing works
Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity
Carroll, B., Maetzel, D., Maddocks, O., Otten, G., Ratcliff, M., Smith, G. R., Dunlop, E., Passos, J., Davies, O. R., Jaenisch, R., et al. (2016) · eLife · doi:10.7554/elife.11058 · Cited by 177 · see citing works
Lysosome: The metabolic signaling hub
Lamming, D. W., & Bar‐Peled, L. (2018) · Traffic · doi:10.1111/tra.12617 · Cited by 183 · see citing works
mTORC1 and Nutrient Homeostasis: The Central Role of the Lysosome
Rabanal-Ruiz, Y., & Korolchuk, V. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030818 · Cited by 159 · see citing works
Regulation of Body Size and Growth Control
Texada, M., Koyama, T., & Rewitz, K. (2020) · Genetics · doi:10.1534/genetics.120.303095 · Cited by 129 · see citing works
Amino acid metabolism, transport and signalling in the liver revisited.
Paulusma, C., Lamers, W., Bröer, S., & van de Graaf, S. V. D. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115074 · Cited by 162 · see citing works
Arginine starvation kills tumor cells through aspartate exhaustion and mitochondrial dysfunction
Cheng, C.-T., Qi, Y., Wang, Y.-C., Chi, K. K., Chung, Y., Ouyang, C., Chen, Y.-R., Oh, M. E., Sheng, X., Tang, Y., et al. (2018) · Communications Biology · doi:10.1038/s42003-018-0178-4 · Cited by 163 · see citing works
The Lysosome Signaling Platform: Adapting With the Times
Inpanathan, S., & Botelho, R. J. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00113 · Cited by 157 · see citing works
The central moTOR of metabolism
Simcox, J., & Lamming, D. W. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.02.024 · Cited by 162 · see citing works
BORC coordinates encounter and fusion of lysosomes with autophagosomes
Jia, R., Guardia, C. M., Pu, J., Chen, Y., & Bonifacino, J. S. (2017) · Autophagy · doi:10.1080/15548627.2017.1343768 · Cited by 160 · see citing works
Ragulator and SLC38A9 activate the Rag GTPases through noncanonical GEF mechanisms
Shen, K., & Sabatini, D. (2018) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1811727115 · Cited by 136 · see citing works
mTORC1 pathway in DNA damage response.
Ma, Y.-X., Vassetzky, Y., & Dokudovskaya, S. (2018) · Biochimica et biophysica acta. Molecular cell research · doi:10.1016/j.bbamcr.2018.06.011 · Cited by 42 · see citing works
mTOR function and therapeutic targeting in breast cancer.
Hare, S. H., & Harvey, A. (2017) · PubMed Central · Cited by 152 · see citing works
The aging lysosome: An essential catalyst for late-onset neurodegenerative diseases
Nixon, R. A. (2020) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2020.140443 · Cited by 149 · see citing works
Regulation of Amino Acid Transport in Saccharomyces cerevisiae
Bianchi, F., Klooster, J. S. V. ’., Ruiz, S. J., & Poolman, B. (2019) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00024-19 · Cited by 142 · see citing works
Regulation of lysosomal ion homeostasis by channels and transporters
Xiong, J., & Zhu, M. X. (2016) · Science China Life Sciences · doi:10.1007/s11427-016-5090-x · Cited by 141 · see citing works
Interactions among mTORC, AMPK and SIRT: a computational model for cell energy balance and metabolism
Sadria, M., & Layton, A. T. (2021) · Cell Communication and Signaling · doi:10.1186/s12964-021-00706-1 · Cited by 141 · see citing works
mTOR: A Cellular Regulator Interface in Health and Disease
Boutouja, F., Stiehm, C. M., & Platta, H. W. (2019) · Cells · doi:10.3390/cells8010018 · Cited by 136 · see citing works
Advances in Autophagy Regulatory Mechanisms
Gallagher, L. E., Williamson, L. E., & Chan, E. Y. W. (2016) · Cells · doi:10.3390/cells5020024 · Cited by 135 · see citing works
Crystal structure of the human lysosomal mTORC1 scaffold complex and its impact on signaling
de Araujo, M. E. G., Naschberger, A., Fürnrohr, B. G., Stasyk, T., Dunzendorfer-Matt, T., Lechner, S., Welti, S., Kremser, L., Shivalingaiah, G., Offterdinger, M., et al. (2017) · Science · doi:10.1126/science.aao1583 · Cited by 134 · see citing works
Quantitative modelling of amino acid transport and homeostasis in mammalian cells
Gauthier-Coles, G., Vennitti, J., Zhang, Z., Comb, W. C., Xing, S., Javed, K., Bröer, A., & Bröer, S. (2021) · Nature Communications · doi:10.1038/s41467-021-25563-x · Cited by 129 · see citing works
A Ragulator–BORC interaction controls lysosome positioning in response to amino acid availability
Pu, J., Keren‐Kaplan, T., & Bonifacino, J. S. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201703094 · Cited by 129 · see citing works
The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging
Fernandes, S., & Demetriades, C. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.707372 · Cited by 124 · see citing works
Systemic tryptophan homeostasis
Klaessens, S., Stroobant, V., de Plaen, E., & den Eynde, B. V. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.897929 · Cited by 110 · see citing works
Lysosome Positioning Influences mTORC2 and AKT Signaling
Jia, R., & Bonifacino, J. S. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.05.009 · Cited by 125 · see citing works
Lysosomes: Signaling Hubs for Metabolic Sensing and Longevity
Savini, M., Zhao, Q., & Wang, M. C. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.08.008 · Cited by 115 · see citing works
LAMTOR/Ragulator is a negative regulator of Arl8b- and BORC-dependent late endosomal positioning
Filipek, P. A., de Araujo, M. E. G., Vogel, G. F., De Smet, C. H., Eberharter, D., Rebsamen, M., Rudashevskaya, E. L., Kremser, L., Yordanov, T., Tschaikner, P., et al. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201703061 · Cited by 119 · see citing works
The role of autophagy in cardiovascular pathology
Gatica, D., Chiong, M., Lavandero, S., & Klionsky, D. J. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab158 · Cited by 120 · see citing works
Macropinocytosis, mTORC1 and cellular growth control
Yoshida, S., Pacitto, R., Inoki, K., & Swanson, J. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2710-y · Cited by 114 · see citing works
Intersubunit Crosstalk in the Rag GTPase Heterodimer Enables mTORC1 to Respond Rapidly to Amino Acid Availability
Shen, K., Choe, A., & Sabatini, D. M. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.09.026 · Cited by 101 · see citing works
Regulation of mTORC1 by Upstream Stimuli
Melick, C. H., & Jewell, J. L. (2020) · Genes · doi:10.3390/genes11090989 · Cited by 80 · see citing works
Leucine induced dephosphorylation of Sestrin2 promotes mTORC1 activation
Kimball, S. R., Gordon, B. S., Moyer, J. E., Dennis, M. D., & Jefferson, L. S. (2016) · Cellular Signalling · doi:10.1016/j.cellsig.2016.03.008 · Cited by 97 · see citing works
Regulatory principles in metabolism–then and now
Curi, R., Newsholme, P., Marzuca-Nassr, G. N., Takahashi, H., Hirabara, S. M., Cruzat, V. F., Krause, M. D. S., & de Bittencourt, P. I. H. (2016) · Biochemical Journal · doi:10.1042/bcj20160103 · Cited by 97 · see citing works
Nutrients: Signal 4 in T cell immunity
Raynor, J. L., & Chi, H. (2024) · The Journal of Experimental Medicine · doi:10.1084/jem.20221839 · Cited by 94 · see citing works
An Arginine Deprivation Response Pathway Is Induced in Leishmania during Macrophage Invasion
Goldman-Pinkovich, A., Balno, C., Strasser, R., Michal, Z.-M., Keren, B., Rentsch, D., Ephros, M. A., Wiese, M., Jardim, A., Myler, P. J., et al. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005494 · Cited by 91 · see citing works
Regulation of metabolic health by essential dietary amino acids
Green, C. L., & Lamming, D. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.07.004 · Cited by 88 · see citing works
Coordination of the leucine-sensing Rag GTPase cycle by leucyl-tRNA synthetase in the mTORC1 signaling pathway
Lee, M.-J., Kim, J. H., Yoon, I., Lee, C., Fallahi-Sichani, M., Kang, J., Kang, J., Guo, M., Lee, K.-Y., Han, G., et al. (2018) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1801287115 · Cited by 82 · see citing works
<scp>GATOR</scp>opathies: The role of amino acid regulatory gene mutations in epilepsy and cortical malformations
Iffland, P. H., Carson, V., Bordey, A., & Crino, P. B. (2019) · Epilepsia · doi:10.1111/epi.16370 · Cited by 84 · see citing works
Sestrin Regulation of TORC1: Is Sestrin a Leucine Sensor?
Lee, J.-H., Cho, U., & Karin, M. (2016) · Science Signaling · doi:10.1126/scisignal.aaf2885 · Cited by 89 · see citing works
mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics
Zhang, H.-X., Xiao, X., Pan, Z.-R., & Dokudovskaya, S. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02493-4 · Cited by 90 · see citing works
Amino Acids Regulate mTORC1 by an Obligate Two-step Mechanism*
Dyachok, J., Earnest, S. A., Iturraran, E. N., Cobb, M., & Ross, E. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.732511 · Cited by 75 · see citing works
SNAT7 is the primary lysosomal glutamine exporter required for extracellular protein-dependent growth of cancer cells
Verdon, Q., Boonen, M., Ribes, C., Jadot, M., Gasnier, B., & Sagné, C. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1617066114 · Cited by 80 · see citing works
Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration
Peng, W., Minakaki, G., Nguyen, M., & Krainc, D. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00742-3 · Cited by 79 · see citing works
Conserved regulators of Rag GTPases orchestrate amino acid-dependent TORC1 signaling
Powis, K., & Virgilio, C. D. (2016) · Cell Discovery · doi:10.1038/celldisc.2015.49 · Cited by 83 · see citing works
The Architecture of the Rag GTPase Signaling Network
Nicastro, R., Sardu, A., Panchaud, N., & VIRGILIO, C. D. (2017) · Biomolecules · doi:10.3390/biom7030048 · Cited by 73 · see citing works
Novel therapeutic approaches targeting L-type amino acid transporters for cancer treatment
Hayashi, K., & Anzai, N. (2017) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v9.i1.21 · Cited by 76 · see citing works
Nutritional Regulation of Gene Expression: Carbohydrate-, Fat- and Amino Acid-Dependent Modulation of Transcriptional Activity
Haro, D., Marrero, P., & Relat, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061386 · Cited by 56 · see citing works
Multiplex image-based autophagy RNAi screening identifies SMCR8 as ULK1 kinase activity and gene expression regulator
Jung, J., Nayak, A., Schaeffer, V., Starzetz, T., Kirsch, A. K., Müller, S. P., Đikić, I., Mittelbronn, M. G. A., & Behrends, C. (2017) · eLife · doi:10.7554/elife.23063 · Cited by 74 · see citing works
Self-citation
Regulation of metabolic health and aging by nutrient-sensitive signaling pathways
Cummings, N. E., & Lamming, D. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.11.014 · Cited by 67 · see citing works
Multifaceted regulation of the system A transporter Slc38a2 suggests nanoscale regulation of amino acid metabolism and cellular signaling
Menchini, R. J., & Chaudhry, F. A. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107789 · Cited by 72 · see citing works
Structural mechanism for amino acid-dependent Rag GTPase nucleotide state switching by SLC38A9
Fromm, S. A., Lawrence, R. E., & Hurley, J. H. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0490-9 · Cited by 72 · see citing works
Dietary restriction of amino acids for Cancer therapy
Kang, J. (2020) · Nutrition & Metabolism · doi:10.1186/s12986-020-00439-x · Cited by 73 · see citing works
Retromer and TBC1D5 maintain late endosomal RAB7 domains to enable amino acid–induced mTORC1 signaling
Kvainickas, A., Nägele, H., Qi, W., Dokládal, L., Jimenez-Orgaz, A., Stehl, L. H., Gangurde, D., Zhao, Q., Hu, Z.-H., Dengjel, J., et al. (2019) · Journal of Cell Biology · doi:10.1083/jcb.201812110 · Cited by 56 · see citing works
Arginine Metabolism and Its Potential in Treatment of Colorectal Cancer
Du, T., & Han, J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.658861 · Cited by 70 · see citing works
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, J., Abeliovich, H., Acevedo‐Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Kölner Universitäts PublikationsServer (Universität zu Köln) · doi:10.5167/uzh-131237 · Cited by 69 · see citing works
The role of mTOR in age-related diseases
Chrienová, Ž., Nepovimová, E., & Kuča, K. (2021) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2021.1955873 · Cited by 68 · see citing works
An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication
Mauthe, M., Langereis, M. A., Jung, J., Zhou, X., Jones, A., Omta, W. A., Tooze, S. A., Stork, B., Paludan, S. R., Ahola, T., et al. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201602046 · Cited by 68 · see citing works
Self-citation
PQLC2 recruits the C9orf72 complex to lysosomes in response to cationic amino acid starvation
Amick, J., Tharkeshwar, A. K., Talaia, G., & Ferguson, S. (2019) · Journal of Cell Biology · doi:10.1083/jcb.201906076 · Cited by 61 · see citing works
The Complex Roles of Mechanistic Target of Rapamycin in Adipocytes and Beyond
Lee, P. L., Jung, S. M., & Guertin, D. A. (2017) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2017.01.004 · Cited by 64 · see citing works
Crystal structure of arginine-bound lysosomal transporter SLC38A9 in the cytosol-open state
Lei, H., Ma, J., Martinez, S. S., & Gonen, T. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0072-2 · Cited by 63 · see citing works

Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1
Plovanich, M. E., Straub, C., Sabatini, B. L., Tsun, Z.-Y., Wang, S., Wolfson, R. L., Shen, K., Wyant, G. A., Yuan, E. D., Jones, T. D., et al. (2014) · DSpace@MIT (Massachusetts Institute of Technology)
The amino acid transporter SLC38A9 is a key component of a lysosomal membrane complex that signals arginine sufficiency to mTORC1
Wang, S., Tsun, Z., Wolfson, R. L., Shen, K., Wyant, G., Plovanich, M. E., Yuan, E. D., Jones, T. D., Chantranupong, L., Comb, W. C., et al. (2015) · Science · doi:10.1126/science.1257132 · Cited by 772 · see citing works
Regulation of amino acid transport across the lysosomal surface by the mTORC1 pathway
Kedir, J. F. (2022) · DSpace@MIT (Massachusetts Institute of Technology)
SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1
Rebsamen, M., Pochini, L., Stasyk, T., de Araújo, M. E. G., Galluccio, M., Kandasamy, R. K., Snijder, B., Fauster, A., Rudashevskaya, E. L., Bruckner, M., et al. (2015) · Nature · doi:10.1038/nature14107 · Cited by 673 · see citing works
Ragulator-Rag Complex Targets mTORC1 to the Lysosomal Surface and Is Necessary for Its Activation by Amino Acids
Sancak, Y., Bar-Peled, L., Zoncu, R., Markhard, A. L., Nada, S., & Sabatini, D. M. (2010) · Cell · doi:10.1016/j.cell.2010.02.024 · Cited by 2,464 · see citing works

Authors: Jung, J., Genau, H. M., & Behrends, C.
Affiliations: Goethe University Frankfurt (DE)
Corresponding author: Behrends, Christian
ORCID: Jung, Jennifer
Behrends, Christian
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 2015-07-01
Volume: 35
Issue: 14
Pages: 2479-2494
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.00125-15
PMC: PMC4475919
OpenAlex: W2257572427
Cited by: 266
References: 55
Citations by year: 2026: 9 · 2025: 11 · 2024: 16 · 2023: 23 · 2022: 23 · 2021: 37 · 2020: 20 · 2019: 28 · 2018: 29 · 2017: 33 · 2016: 30 · 2015: 6 · 2014: 1
FWCI: 14.19
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft (BE 4685/1‐1)
FP7 Ideas: European Research Council (282333)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: SLC38A9, mTORC1, Rag GTPases, amino acid signaling, lysosomes, Rheb, amino acid starvation, transmembrane proteins, translational regulation
MeSH terms: Ras Homolog Enriched in Brain Protein, Mechanistic Target of Rapamycin Complex 1, Amino Acids, Fluorescent Antibody Technique, Humans, Lysosomes, Neuropeptides, Protein Binding, Immunoblotting, GTP Phosphohydrolases, Monomeric GTP-Binding Proteins, Amino Acid Transport Systems, RNA Interference, Multiprotein Complexes, HEK293 Cells, TOR Serine-Threonine Kinases, Protein Interaction Maps

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Amino Acid-Dependent mTORC1 Regulation by the Lysosomal Membrane Protein SLC38A9

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks