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

REFERENCES

• Guertin DA, Sabatini DM. 2007. Defining the role of mTOR in cancer. Cancer Cell 12:9–22. http://dx.doi.org/10.1016/j.ccr.2007.05.008.
   PubMed Web of Science ®Google Scholar
• Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM. 2002. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110:163–175. http://dx.doi.org/10.1016/S0092-8674(02)00808-5.
   PubMed Web of Science ®Google Scholar
• Kim DH, Sarbassov DD, Ali SM, Latek RR, Guntur KV, Erdjument-Bromage H, Tempst P, Sabatini DM. 2003. GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell 11:895–904. http://dx.doi.org/10.1016/S1097-2765(03)00114-X.
   PubMed Web of Science ®Google Scholar
• Sengupta S, Peterson TR, Sabatini DM. 2010. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell 40:310–322. http://dx.doi.org/10.1016/j.molcel.2010.09.026.
   PubMed Web of Science ®Google Scholar
• Dibble CC, Elis W, Menon S, Qin W, Klekota J, Asara JM, Finan PM, Kwiatkowski DJ, Murphy LO, Manning BD. 2012. TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1. Mol Cell 47:535–546. http://dx.doi.org/10.1016/j.molcel.2012.06.009.
   PubMed Web of Science ®Google Scholar
• Inoki K, Li Y, Xu T, Guan KL. 2003. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev 17:1829–1834. http://dx.doi.org/10.1101/gad.1110003.
   PubMed Web of Science ®Google Scholar
• Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J. 2003. Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol 13:1259–1268. http://dx.doi.org/10.1016/S0960-9822(03)00506-2.
   PubMed Web of Science ®Google Scholar
• Groenewoud MJ, Zwartkruis FJ. 2013. Rheb and Rags come together at the lysosome to activate mTORC1. Biochem Soc Trans 41:951–955. http://dx.doi.org/10.1042/BST20130037.
   PubMedGoogle Scholar
• Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, Sabatini DM. 2008. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320:1496–1501. http://dx.doi.org/10.1126/science.1157535.
   PubMed Web of Science ®Google Scholar
• Saito K, Araki Y, Kontani K, Nishina H, Katada T. 2005. Novel role of the small GTPase Rheb: its implication in endocytic pathway independent of the activation of mammalian target of rapamycin. J Biochem 137:423–430. http://dx.doi.org/10.1093/jb/mvi046.
   PubMedGoogle Scholar
• Buerger C, DeVries B, Stambolic V. 2006. Localization of Rheb to the endomembrane is critical for its signaling function. Biochem Biophys Res Commun 344:869–880. http://dx.doi.org/10.1016/j.bbrc.2006.03.220.
   PubMedGoogle Scholar
• Castro AF, Rebhun JF, Clark GJ, Quilliam LA. 2003. Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner. J Biol Chem 278:32493–32496. http://dx.doi.org/10.1074/jbc.C300226200.
   PubMed Web of Science ®Google Scholar
• Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J. 2005. Rheb binds and regulates the mTOR kinase. Curr Biol 15:702–713. http://dx.doi.org/10.1016/j.cub.2005.02.053.
   PubMed Web of Science ®Google Scholar
• Yadav RB, Burgos P, Parker AW, Iadevaia V, Proud CG, Allen RA, O'Connell JP, Jeshtadi A, Stubbs CD, Botchway SW. 2013. mTOR direct interactions with Rheb-GTPase and raptor: sub-cellular localization using fluorescence lifetime imaging. BMC Cell Biol 14:3. http://dx.doi.org/10.1186/1471-2121-14-3.
   PubMedGoogle Scholar
• Hara K, Yonezawa K, Weng QP, Kozlowski MT, Belham C, Avruch J. 1998. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol Chem 273:14484–14494. http://dx.doi.org/10.1074/jbc.273.23.14484.
   PubMed Web of Science ®Google Scholar
• Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM. 2010. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141:290–303. http://dx.doi.org/10.1016/j.cell.2010.02.024.
   PubMed Web of Science ®Google Scholar
• Kim MS, Kuehn HS, Metcalfe DD, Gilfillan AM. 2008. Activation and function of the mTORC1 pathway in mast cells. J Immunol 180:4586–4595. http://dx.doi.org/10.4049/jimmunol.180.7.4586.
   PubMedGoogle Scholar
• Sekiguchi T, Hirose E, Nakashima N, Ii M, Nishimoto T. 2001. Novel G proteins, Rag C and Rag D, interact with GTP-binding proteins, Rag A and Rag B. J Biol Chem 276:7246–7257. http://dx.doi.org/10.1074/jbc.M004389200.
   PubMed Web of Science ®Google Scholar
• Schurmann A, Brauers A, Massmann S, Becker W, Joost HG. 1995. Cloning of a novel family of mammalian GTP-binding proteins (RagA, RagBs, RagB1) with remote similarity to the Ras-related GTPases. J Biol Chem 270:28982–28988. http://dx.doi.org/10.1074/jbc.270.48.28982.
   PubMed Web of Science ®Google Scholar
• Tsun ZY, Bar-Peled L, Chantranupong L, Zoncu R, Wang T, Kim C, Spooner E, Sabatini DM. 2013. The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1. Mol Cell 52:495–505. http://dx.doi.org/10.1016/j.molcel.2013.09.016.
   PubMed Web of Science ®Google Scholar
• Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA, Grabiner BC, Spear ED, Carter SL, Meyerson M, Sabatini DM. 2013. A tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science 340:1100–1106. http://dx.doi.org/10.1126/science.1232044.
   PubMed Web of Science ®Google Scholar
• Han JM, Jeong SJ, Park MC, Kim G, Kwon NH, Kim HK, Ha SH, Ryu SH, Kim S. 2012. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 149:410–424. http://dx.doi.org/10.1016/j.cell.2012.02.044.
   PubMed Web of Science ®Google Scholar
• Bar-Peled L, Schweitzer LD, Zoncu R, Sabatini DM. 2012. Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. Cell 150:1196–1208. http://dx.doi.org/10.1016/j.cell.2012.07.032.
   PubMed Web of Science ®Google Scholar
• Zoncu R, Bar-Peled L, Efeyan A, Wang S, Sancak Y, Sabatini DM. 2011. mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science 334:678–683. http://dx.doi.org/10.1126/science.1207056.
   PubMed Web of Science ®Google Scholar
• Rebsamen M, Pochini L, Stasyk T, de Araujo ME, Galluccio M, Kandasamy RK, Snijder B, Fauster A, Rudashevskaya EL, Bruckner M, Scorzoni S, Filipek PA, Huber KV, Bigenzahn JW, Heinz LX, Kraft C, Bennett KL, Indiveri C, Huber LA, Superti-Furga G. 2015. SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Nature 519:477–481. http://dx.doi.org/10.1038/nature14107.
   PubMed Web of Science ®Google Scholar
• Wang S, Tsun ZY, Wolfson RL, Shen K, Wyant GA, Plovanich ME, Yuan ED, Jones TD, Chantranupong L, Comb W, Wang T, Bar-Peled L, Zoncu R, Straub C, Kim C, Park J, Sabatini BL, Sabatini DM. 2015. Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science 347:188–194. http://dx.doi.org/10.1126/science.1257132.
   PubMed Web of Science ®Google Scholar
• Behrends C, Sowa ME, Gygi SP, Harper JW. 2010. Network organization of the human autophagy system. Nature 466:68–76. http://dx.doi.org/10.1038/nature09204.
   PubMed Web of Science ®Google Scholar
• Sowa ME, Bennett EJ, Gygi SP, Harper JW. 2009. Defining the human deubiquitinating enzyme interaction landscape. Cell 138:389–403. http://dx.doi.org/10.1016/j.cell.2009.04.042.
   PubMed Web of Science ®Google Scholar
• Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP. 2010. A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143:1174–1189. http://dx.doi.org/10.1016/j.cell.2010.12.001.
   PubMed Web of Science ®Google Scholar
• Smith EM, Finn SG, Tee AR, Browne GJ, Proud CG. 2005. The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses. J Biol Chem 280:18717–18727. http://dx.doi.org/10.1074/jbc.M414499200.
   PubMed Web of Science ®Google Scholar
• Demetriades C, Doumpas N, Teleman AA. 2014. Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2. Cell 156:786–799. http://dx.doi.org/10.1016/j.cell.2014.01.024.
   PubMed Web of Science ®Google Scholar
• Krogh A, Larsson B, von Heijne G, Sonnhammer EL. 2001. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 305:567–580. http://dx.doi.org/10.1006/jmbi.2000.4315.
   PubMed Web of Science ®Google Scholar
• Korolchuk VI, Saiki S, Lichtenberg M, Siddiqi FH, Roberts EA, Imarisio S, Jahreiss L, Sarkar S, Futter M, Menzies FM, O'Kane CJ, Deretic V, Rubinsztein DC. 2011. Lysosomal positioning coordinates cellular nutrient responses. Nat Cell Biol 13:453–460. http://dx.doi.org/10.1038/ncb2204.
   PubMed Web of Science ®Google Scholar
• Schioth HB, Roshanbin S, Hagglund MG, Fredriksson R. 2013. Evolutionary origin of amino acid transporter families SLC32, SLC36 and SLC38 and physiological, pathological and therapeutic aspects. Mol Aspects Med 34:571–585. http://dx.doi.org/10.1016/j.mam.2012.07.012.
   PubMed Web of Science ®Google Scholar
• Fletcher JS, Beevers H. 1971. Influence of cycloheximide on the synthesis and utilization of amino acids in suspension cultures. Plant Physiol 48:261–264. http://dx.doi.org/10.1104/pp.48.3.261.
   PubMedGoogle Scholar
• Widuczynski I, Stoppani AO. 1965. Action of cycloheximide on amino acid metabolism in Saccharomyces elipsoideus. Biochim Biophys Acta 104:413–426. http://dx.doi.org/10.1016/0304-4165(65)90347-8.
   PubMedGoogle Scholar
• Beugnet A, Tee AR, Taylor PM, Proud CG. 2003. Regulation of targets of mTOR (mammalian target of rapamycin) signalling by intracellular amino acid availability. Biochem J 372:555–566. http://dx.doi.org/10.1042/BJ20021266.
   PubMed Web of Science ®Google Scholar
• Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, Yang H, Hild M, Kung C, Wilson C, Myer VE, MacKeigan JP, Porter JA, Wang YK, Cantley LC, Finan PM, Murphy LO. 2009. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 136:521–534. http://dx.doi.org/10.1016/j.cell.2008.11.044.
   PubMed Web of Science ®Google Scholar
• Wang X, Campbell LE, Miller CM, Proud CG. 1998. Amino acid availability regulates p70 S6 kinase and multiple translation factors. Biochem J 334(Part 1):261–267.
   PubMedGoogle Scholar
• Pinilla J, Aledo JC, Cwiklinski E, Hyde R, Taylor PM, Hundal HS. 2011. SNAT2 transceptor signalling via mTOR: a role in cell growth and proliferation? Front Biosci 3:1289–1299. http://dx.doi.org/10.2741/332.
   Google Scholar
• Sagne C, Agulhon C, Ravassard P, Darmon M, Hamon M, El Mestikawy S, Gasnier B, Giros B. 2001. Identification and characterization of a lysosomal transporter for small neutral amino acids. Proc Natl Acad Sci U S A 98:7206–7211. http://dx.doi.org/10.1073/pnas.121183498.
   PubMed Web of Science ®Google Scholar
• Agulhon C, Rostaing P, Ravassard P, Sagne C, Triller A, Giros B. 2003. Lysosomal amino acid transporter LYAAT-1 in the rat central nervous system: an in situ hybridization and immunohistochemical study. J Comp Neurol 462:71–89. http://dx.doi.org/10.1002/cne.10712.
   PubMedGoogle Scholar
• Ogmundsdottir MH, Heublein S, Kazi S, Reynolds B, Visvalingam SM, Shaw MK, Goberdhan DC. 2012. Proton-assisted amino acid transporter PAT1 complexes with Rag GTPases and activates TORC1 on late endosomal and lysosomal membranes. PLoS One 7:e36616. http://dx.doi.org/10.1371/journal.pone.0036616.
   PubMedGoogle Scholar
• Edwards N, Anderson CM, Gatfield KM, Jevons MP, Ganapathy V, Thwaites DT. 2011. Amino acid derivatives are substrates or non-transported inhibitors of the amino acid transporter PAT2 (slc36a2). Biochim Biophys Acta 1808:260–270. http://dx.doi.org/10.1016/j.bbamem.2010.07.032.
   PubMedGoogle Scholar
• Sugawara M, Nakanishi T, Fei YJ, Huang W, Ganapathy ME, Leibach FH, Ganapathy V. 2000. Cloning of an amino acid transporter with functional characteristics and tissue expression pattern identical to that of system A. J Biol Chem 275:16473–16477. http://dx.doi.org/10.1074/jbc.C000205200.
   PubMed Web of Science ®Google Scholar
• Yao D, Mackenzie B, Ming H, Varoqui H, Zhu H, Hediger MA, Erickson JD. 2000. A novel system A isoform mediating Na+/neutral amino acid cotransport. J Biol Chem 275:22790–22797. http://dx.doi.org/10.1074/jbc.M002965200.
   PubMed Web of Science ®Google Scholar
• Hatanaka T, Huang W, Ling R, Prasad PD, Sugawara M, Leibach FH, Ganapathy V. 2001. 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. Biochim Biophys Acta 1510:10–17. http://dx.doi.org/10.1016/S0005-2736(00)00390-4.
   PubMed Web of Science ®Google Scholar
• Sugawara M, Nakanishi T, Fei YJ, Martindale RG, Ganapathy ME, Leibach FH, Ganapathy V. 2000. Structure and function of ATA3, a new subtype of amino acid transport system A, primarily expressed in the liver and skeletal muscle. Biochim Biophys Acta 1509:7–13. http://dx.doi.org/10.1016/S0005-2736(00)00349-7.
   PubMedGoogle Scholar
• Chaudhry FA, Reimer RJ, Krizaj D, Barber D, Storm-Mathisen J, Copenhagen DR, Edwards RH. 1999. Molecular analysis of system N suggests novel physiological roles in nitrogen metabolism and synaptic transmission. Cell 99:769–780. http://dx.doi.org/10.1016/S0092-8674(00)81674-8.
   PubMedGoogle Scholar
• Nakanishi T, Kekuda R, Fei YJ, Hatanaka T, Sugawara M, Martindale RG, Leibach FH, Prasad PD, Ganapathy V. 2001. Cloning and functional characterization of a new subtype of the amino acid transport system. N Am J Physiol Cell Physiol 281:C1757–C1768.
   PubMed Web of Science ®Google Scholar
• Varoqui H, Zhu H, Yao D, Ming H, Erickson JD. 2000. Cloning and functional identification of a neuronal glutamine transporter. J Biol Chem 275:4049–4054. http://dx.doi.org/10.1074/jbc.275.6.4049.
   PubMed Web of Science ®Google Scholar
• Hagglund MG, Sreedharan S, Nilsson VC, Shaik JH, Almkvist IM, Backlin S, Wrange O, Fredriksson R. 2011. Identification of SLC38A7 (SNAT7) protein as a glutamine transporter expressed in neurons. J Biol Chem 286:20500–20511. http://dx.doi.org/10.1074/jbc.M110.162404.
   PubMed Web of Science ®Google Scholar
• Heuser J. 1989. Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH. J Cell Biol 108:855–864. http://dx.doi.org/10.1083/jcb.108.3.855.
   PubMed Web of Science ®Google Scholar
• Yildirim MA, Goh KI, Cusick ME, Barabasi AL, Vidal M. 2007. Drug-target network. Nat Biotechnol 25:1119–1126. http://dx.doi.org/10.1038/nbt1338.
   PubMed Web of Science ®Google Scholar