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SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1
Open accessAbstract
Cell growth and proliferation are tightly linked to nutrient availability. The mechanistic target of rapamycin complex 1 (mTORC1) integrates the presence of growth factors, energy levels, glucose and amino acids to modulate metabolic status and cellular responses. mTORC1 is activated at the surface of lysosomes by the RAG GTPases and the Ragulator complex through a not fully understood mechanism monitoring amino acid availability in the lysosomal lumen and involving the vacuolar H(+)-ATPase. Here we describe the uncharacterized human member 9 of the solute carrier family 38 (SLC38A9) as a lysosomal membrane-resident protein competent in amino acid transport. Extensive functional proteomic analysis established SLC38A9 as an integral part of the Ragulator-RAG GTPases machinery. Gain of SLC38A9 function rendered cells resistant to amino acid withdrawal, whereas loss of SLC38A9 expression impaired amino-acid-induced mTORC1 activation. Thus SLC38A9 is a physical and functional component of the amino acid sensing machinery that controls the activation of mTOR.
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“The membrane-resident amino acid transporter SLC38A9 is a key component of this sensing machinery (452).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [452]
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“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 Rebsamen et al., 2015
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Cites
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509
Membrane transporters in drug development
The International Transporter Consortium, Giacomini, K. M., Huang, S.-M., Tweedie, D. J., Benet, L. Z., Brouwer, K. L. R., Chu, X., Dahlin, A., Evers, R., Fischer, V., et al. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3028 · Cited by 3,340
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
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
Towards a knowledge-based Human Protein Atlas
Uhlen, M., Oksvold, P., Fagerberg, L., Lundberg, E., Jonasson, K., Forsberg, M., Zwahlen, M., Kampf, C., Wester, K., Hober, S., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt1210-1248 · Cited by 2,440
A lysosome‐to‐nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB
Settembre, C., Zoncu, R., Medina, D. L., Vetrini, F., Erdin, S., Erdin, S., Huynh, T., Ferron, M., Karsenty, G., Vellard, M. C., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.32 · Cited by 1,920
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
The CRAPome: a contaminant repository for affinity purification–mass spectrometry data
Mellacheruvu, D., Wright, Z., Couzens, A. L., Lambert, J.-P., St-Denis, N. A., Li, T., Miteva, Y. V., Hauri, S., Sardiu, M. E., Low, T. Y., et al. (2013) · Nature Methods · doi:10.1038/nmeth.2557 · Cited by 1,686
Self-citationZoncu, R., Bar-Peled, L., Efeyan, A., Wang, S., Sancak, Y., & Sabatini, D. M. (2011) · Science · doi:10.1126/science.1207056 · Cited by 1,673
Regulation of TORC1 by Rag GTPases in nutrient response
Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P., & Guan, K.-L. (2008) · Nature Cell Biology · doi:10.1038/ncb1753 · Cited by 1,349
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
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
Amino acid signalling upstream of mTOR
Jewell, J. L., Russell, R. C., & Guan, K.-L. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3522 · Cited by 894
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
SAINT: probabilistic scoring of affinity purification–mass spectrometry data
Choi, H., Larsen, B., Lin, Z.-Y., Breitkreutz, A., Mellacheruvu, D., Fermin, D., Qin, Z. S., Tyers, M., Gingras, A.-C., & Nesvizhskii, A. I. (2011) · Nature Methods · doi:10.1038/nmeth.1541 · Cited by 800
Glutaminolysis Activates Rag-mTORC1 Signaling
Durán, R. V., Oppliger, W., Robitaille, A. M., Heiserich, L., Skendaj, R., Gottlieb, E., & Hall, M. N. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.05.043 · Cited by 766
Signal integration by mTORC1 coordinates nutrient input with biosynthetic output
Dibble, C. C., & Manning, B. D. (2013) · Nature Cell Biology · doi:10.1038/ncb2763 · Cited by 743
The ABCs of membrane transporters in health and disease (SLC series): Introduction
Hediger, M. A., Clémençon, B., Burrier, R. E., & Bruford, E. A. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.12.009 · Cited by 647
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
mTOR in aging, metabolism, and cancer
Cornu, M., Albert, V., & Hall, M. N. (2013) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2012.12.005 · Cited by 455
Population context determines cell-to-cell variability in endocytosis and virus infection
Snijder, B., Sacher, R., Rämö, P., Damm, E.-M., Liberali, P., & Pelkmans, L. (2009) · Nature · doi:10.1038/nature08282 · Cited by 399
Self-citationOLAV: Towards high‐throughput tandem mass spectrometry data identification
Colinge, J., Masselot, A., Giron, M., Dessingy, T., & Magnin, J. (2003) · PROTEOMICS · doi:10.1002/pmic.200300485 · Cited by 297
Panchaud, N., Péli-Gulli, M.-P., & De Virgilio, C. (2013) · Science Signaling · doi:10.1126/scisignal.2004112 · Cited by 286
Viral immune modulators perturb the human molecular network by common and unique strategies
Pichlmair, A., Kandasamy, K., Alvisi, G., Mulhern, O., Sacco, R., Habjan, M., Binder, M., Stefanovic, A., Eberle, C.-A., Goncalves, A., et al. (2012) · Nature · doi:10.1038/nature11289 · Cited by 262
Self-citationAn Extended Proteome Map of the Lysosomal Membrane Reveals Novel Potential Transporters
Chapel, A., Kieffer‐Jaquinod, S., Sagné, C., Verdon, Q., Ivaldi, C., Mellal, M., Thirion, J., Jadot, M., Bruley, C., Garin, J., et al. (2013) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.021980 · Cited by 209
Interlaboratory reproducibility of large-scale human protein-complex analysis by standardized AP-MS
Varjosalo, M. T., Sacco, R., Stukalov, A., van Drogen, A., Planyavsky, M., Hauri, S., Aebersold, R. H., Bennett, K. L., Colinge, J., Gstaiger, M., et al. (2013) · Nature Methods · doi:10.1038/nmeth.2400 · Cited by 208
Self-citationGoberdhan, D. C. I., Meredith, D., Boyd, C. A. R., & WILSON, C. G. (2005) · Development · doi:10.1242/dev.01821 · Cited by 159
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
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 149
Amino-acid-induced signalling via the SPS-sensing pathway in yeast
Ljungdahl, P. O. (2009) · Biochemical Society Transactions · doi:10.1042/bst0370242 · Cited by 132
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 128
Bennett, K. L., Funk, M., Tschernutter, M., Breitwieser, F. P., Planyavsky, M., Ubaida‐Mohien, C., Müller, A. C., Trajanoski, Z., Colinge, J., Superti‐Furga, G., et al. (2010) · Journal of Proteomics · doi:10.1016/j.jprot.2010.10.002 · Cited by 87
Self-citationCompetitive intra- and extracellular nutrient sensing by the transporter homologue Ssy1p
Wu, B., Ottow, K. E., Poulsen, P., Gaber, R. F., Albers, E., & Kielland‐Brandt, M. C. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200602089 · Cited by 78
Kriel, J., Haesendonckx, S., Rubio‐Texeira, M., Zeebroeck, G. V., & Thevelein, J. M. (2011) · BioEssays · doi:10.1002/bies.201100100 · Cited by 78
Pochini, L., Scalise, M., Galluccio, M., Amelio, L., & Indiveri, C. (2011) · Biochemical Journal · doi:10.1042/bj20110544 · Cited by 42
Self-citationAmino acid transporters: éminences grises of nutrient signalling mechanisms?
Taylor, P. M. (2009) · Biochemical Society Transactions · doi:10.1042/bst0370237 · Cited by 40
Zhang, Z., Gameiro, A. M., & Grewer, C. T. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m706774200 · Cited by 29
Over-expression in E. coli and purification of the human OCTN1 transport protein
Galluccio, M., Pochini, L., Amelio, L., Accardi, R., Tommasino, M., & Indiveri, C. (2009) · Protein Expression and Purification · doi:10.1016/j.pep.2009.06.015 · Cited by 23
Self-citationAffinity Purification Strategies for Proteomic Analysis of Transcription Factor Complexes
Giambruno, R., Grebien, F., Stukalov, A., Knöll, C., Planyavsky, M., Rudashevskaya, E. L., Colinge, J., Superti‐Furga, G., & Bennett, K. L. (2013) · Journal of Proteome Research · doi:10.1021/pr4003323 · Cited by 20
Self-citationOppedisano, F., Pochini, L., Bröer, S., & Indiveri, C. (2011) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2011.05.011 · Cited by 17
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Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.02.004 · Cited by 7,555
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
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Self-citationmTOR at the nexus of nutrition, growth, ageing and disease
Liu, G. Y., & Sabatini, D. M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0199-y · Cited by 2,737
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
Metadata
- Authors
- 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., Scorzoni, S., Filipek, P. A., Huber, K. V. M., Bigenzahn, J. W., Heinz, L. X., Kraft, C., Bennett, K. L., Indiveri, C., Huber, L. A., & Superti-Furga, G.
- Affiliations
- Austrian Academy of Sciences (AT)
- University of Calabria (IT)
- Innsbruck Medical University (AT)
- University of Vienna (AT)
- ORCID
- Venue
- Nature
- Published
- 2015-01-07
- Volume
- 519
- Issue
- 7544
- Pages
- 477-481
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4376665
- OpenAlex
- W2093154482
- Cited by
- 673
- References
- 40
- Citations by year
- 2026: 32 · 2025: 47 · 2024: 34 · 2023: 45 · 2022: 55 · 2021: 91 · 2020: 57 · 2019: 50 · 2018: 65 · 2017: 60 · 2016: 76 · 2015: 59
- FWCI
- 37.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (HIR 10-001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- SLC38A9, mTORC1, amino acid sensing, lysosomes, Ragulator complex, Rag GTPases, amino acid transport, lysosomal membrane proteins, nutrient signaling, cell growth and proliferation
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Amino Acids, Animals, Cell Line, Humans, Lysosomes, Nucleotides, Monomeric GTP-Binding Proteins, Amino Acid Transport Systems, Multiprotein Complexes, Mice, TOR Serine-Threonine Kinases
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