The DOI matches its Crossref record; 55 of the 56 references it cites were found in a registry or an index, and 1 are not checked yet.
Amino Acid-Dependent mTORC1 Regulation by the Lysosomal Membrane Protein SLC38A9
Open accessAbstract
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.
Overview
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
Cites
Statistics
Verification
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?
In the citing paper
“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.
Citations
Cites
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
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 3,551
Kim, D., Sarbassov, D. D., Ali, S. M., King, J. E., Latek, R. R., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 3,051
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
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 · cited 13×
“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).”
BackgroundInfluentialRheb 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
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
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
Yıldırım, M. A., Goh, K.-I., Cusick, M. E., Barabási, A.-Ĺ., & Vidal, M. (2007) · Nature Biotechnology · doi:10.1038/nbt1338 · Cited by 1,744
Research works printed but not linked: 1
- Pinilla J, 2011, Front Biosci, 3, 1289
Cited by
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
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
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
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 1,094
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
Metadata
- Authors
- Jung, J., Genau, H. M., & Behrends, C.
- Affiliations
- Goethe University Frankfurt (DE)
- Corresponding author
- 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
- 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
- FWCI
- 14.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- 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
- 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, 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
