Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome

Cell

Volumn 156, Issue 4, 2014, Pages 771-785

  Menon, Suchithra ^a   Dibble, Christian C ^b   Talbott, George ^a   Hoxhaj, Gerta ^a   Valvezan, Alexander J ^a   Takahashi, Hidenori ^b   Cantley, Lewis C ^b,c   Manning, Brendan D ^a  

^a HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

8 [4 (1 AMINOCYCLOBUTYL)PHENYL] 9 PHENYL 1,2,4 TRIAZOLO[3,4 F][1,6]NAPHTHYRIDIN 3(2H) ONE; CORE PROTEIN; INSULIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; RHEB PROTEIN; TUBEROUS SCLEROSIS COMPLEX PROTEIN; UNCLASSIFIED DRUG; WORTMANNIN; PHOSPHATIDYLINOSITOL 3 KINASE;

ARTICLE; CELL SUBPOPULATION; CELLULAR DISTRIBUTION; CONTROLLED STUDY; DISSOCIATION; GEL PERMEATION CHROMATOGRAPHY; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOFLUORESCENCE; KWASHIORKOR; LYSOSOME; MOLECULAR WEIGHT; MYRISTYLATION; NUTRIENT; PALMITOYLATION; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN QUATERNARY STRUCTURE; SIGNAL TRANSDUCTION; CELL GROWTH; TUBEROUS SCLEROSIS;

AMINO ACIDS; ANIMALS; CELL LINE; GTP PHOSPHOHYDROLASES; HUMANS; INSULIN; LYSOSOMES; MICE; MULTIPROTEIN COMPLEXES; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHORYLATION; TOR SERINE-THREONINE KINASES; TUMOR SUPPRESSOR PROTEINS;

EID: 84894114029     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2013.11.049     Document Type: Article

References (51)

1. L. Bar-Peled, L.D. Schweitzer, R. Zoncu, and D.M. Sabatini Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1 Cell 150 2012 1196 1208
2. L. Bar-Peled, L. Chantranupong, A.D. Cherniack, W.W. Chen, K.A. Ottina, B.C. Grabiner, E.D. Spear, S.L. Carter, M. Meyerson, and D.M. Sabatini A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1 Science 340 2013 1100 1106
3. J.L. Bos, H. Rehmann, and A. Wittinghofer GEFs and GAPs: critical elements in the control of small G proteins Cell 129 2007 865 877 (Pubitemid 46802708)
4. C. Buerger, B. DeVries, and V. Stambolic Localization of Rheb to the endomembrane is critical for its signaling function Biochem. Biophys. Res. Commun. 344 2006 869 880
5. S.L. Cai, A.R. Tee, J.D. Short, J.M. Bergeron, J. Kim, J. Shen, R. Guo, C.L. Johnson, K. Kiguchi, and C.L. Walker Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning J. Cell Biol. 173 2006 279 289
6. J.M. Capo-Chichi, J. Tcherkezian, F.F. Hamdan, J.C. Décarie, S. Dobrzeniecka, L. Patry, M.A. Nadon, B.E. Mucha, P. Major, and M. Shevell et al. Disruption of TBC1D7, a subunit of the TSC1-TSC2 protein complex, in intellectual disability and megalencephaly J. Med. Genet. 50 2013 740 744
7. A.F. Castro, J.F. Rebhun, G.J. Clark, and L.A. Quilliam Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner J. Biol. Chem. 278 2003 32493 32496 (Pubitemid 37055685)
8. X.W. Chen, D. Leto, T. Xiong, G. Yu, A. Cheng, S. Decker, and A.R. Saltiel A Ral GAP complex links PI 3-kinase/Akt signaling to RalA activation in insulin action Mol. Biol. Cell 22 2011 141 152
9. G.J. Clark, M.S. Kinch, K. Rogers-Graham, S.M. Sebti, A.D. Hamilton, and C.J. Der The Ras-related protein Rheb is farnesylated and antagonizes Ras signaling and transformation J. Biol. Chem. 272 1997 10608 10615 (Pubitemid 27181069)
10. B. Cool, B. Zinker, W. Chiou, L. Kifle, N. Cao, M. Perham, R. Dickinson, A. Adler, G. Gagne, and R. Iyengar et al. Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome Cell Metab. 3 2006 403 416 (Pubitemid 43811782)
11. P.B. Crino, K.L. Nathanson, and E.P. Henske The tuberous sclerosis complex N. Engl. J. Med. 355 2006 1345 1356
12. H.C. Dan, M. Sun, L. Yang, R.I. Feldman, X.M. Sui, C.C. Ou, M. Nellist, R.S. Yeung, D.J. Halley, and S.V. Nicosia et al. Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin J. Biol. Chem. 277 2002 35364 35370
13. O. Daumke, M. Weyand, P.P. Chakrabarti, I.R. Vetter, and A. Wittinghofer The GTPase-activating protein Rap1GAP uses a catalytic asparagine Nature 429 2004 197 201 (Pubitemid 38656197)
14. C. Demetriades, N. Doumpas, and A.A. Teleman Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2 Cell 156 2014 786 799 this issue
15. C.C. Dibble, and B.D. Manning Signal integration by mTORC1 coordinates nutrient input with biosynthetic output Nat. Cell Biol. 15 2013 555 564
16. C.C. Dibble, W. Elis, S. Menon, W. Qin, J. Klekota, J.M. Asara, P.M. Finan, D.J. Kwiatkowski, L.O. Murphy, and B.D. Manning TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1 Mol. Cell 47 2012 535 546
17. J. Dong, and D. Pan Tsc2 is not a critical target of Akt during normal Drosophila development Genes Dev. 18 2004 2479 2484 (Pubitemid 39362890)
18. K. Hara, K. Yonezawa, Q.P. Weng, M.T. Kozlowski, C. Belham, and J. Avruch Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism J. Biol. Chem. 273 1998 14484 14494 (Pubitemid 28319170)
19. M. Hoogeveen-Westerveld, R. Ekong, S. Povey, I. Karbassi, S.D. Batish, J.T. den Dunnen, A. van Eeghen, E. Thiele, K. Mayer, and K. Dies et al. Functional assessment of TSC1 missense variants identified in individuals with tuberous sclerosis complex Hum. Mutat. 33 2012 476 479
20. M. Hoogeveen-Westerveld, L. van Unen, A. van den Ouweland, D. Halley, A. Hoogeveen, and M. Nellist The TSC1-TSC2 complex consists of multiple TSC1 and TSC2 subunits BMC Biochem. 13 2012 18
21. M. Hoogeveen-Westerveld, R. Ekong, S. Povey, K. Mayer, N. Lannoy, F. Elmslie, M. Bebin, K. Dies, C. Thompson, and S.P. Sparagana et al. Functional assessment of TSC2 variants identified in individuals with tuberous sclerosis complex Hum. Mutat. 34 2013 167 175
22. J.J. Howell, S.J. Ricoult, I. Ben-Sahra, and B.D. Manning A growing role for mTOR in promoting anabolic metabolism Biochem. Soc. Trans. 41 2013 906 912
23. K. Inoki, Y. Li, T. Zhu, J. Wu, and K.L. Guan TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling Nat. Cell Biol. 4 2002 648 657 (Pubitemid 34993700)
24. B.L. Jacobs, J.S. You, J.W. Frey, C.A. Goodman, D.M. Gundermann, and T.A. Hornberger Eccentric contractions increase TSC2 phosphorylation and alter the targeting of TSC2 and mTOR to the lysosome J. Physiol. 591 2013 4611 4620
25. D.H. Kim, D.D. Sarbassov, S.M. Ali, J.E. King, R.R. Latek, H. Erdjument-Bromage, P. Tempst, and D.M. Sabatini mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery Cell 110 2002 163 175 (Pubitemid 34876545)
26. E. Kim, P. Goraksha-Hicks, L. Li, T.P. Neufeld, and K.L. Guan Regulation of TORC1 by Rag GTPases in nutrient response Nat. Cell Biol. 10 2008 935 945
27. V.I. Korolchuk, S. Saiki, M. Lichtenberg, F.H. Siddiqi, E.A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, and F.M. Menzies et al. Lysosomal positioning coordinates cellular nutrient responses Nat. Cell Biol. 13 2011 453 460
28. M. Laplante, and D.M. Sabatini mTOR signaling in growth control and disease Cell 149 2012 274 293
29. X. Long, Y. Lin, S. Ortiz-Vega, K. Yonezawa, and J. Avruch Rheb binds and regulates the mTOR kinase Curr. Biol. 15 2005 702 713 (Pubitemid 40599924)
30. B.D. Manning, A.R. Tee, M.N. Logsdon, J. Blenis, and L.C. Cantley Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway Mol. Cell 10 2002 151 162 (Pubitemid 34876569)
31. S. Menon, and B.D. Manning Common corruption of the mTOR signaling network in human tumors Oncogene 27 Suppl 2 2008 S43 S51
32. C.P. Mîinea, H. Sano, S. Kane, E. Sano, M. Fukuda, J. Peränen, W.S. Lane, and G.E. Lienhard AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain Biochem. J. 391 2005 87 93 (Pubitemid 41445479)
33. S. Nada, A. Hondo, A. Kasai, M. Koike, K. Saito, Y. Uchiyama, and M. Okada The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK-ERK pathway to late endosomes EMBO J. 28 2009 477 489
34. M. Nellist, O. Sancak, M.A. Goedbloed, C. Rohe, D. van Netten, K. Mayer, A. Tucker-Williams, A.M. van den Ouweland, and D.J. Halley Distinct effects of single amino-acid changes to tuberin on the function of the tuberin-hamartin complex Eur. J. Hum. Genet. 13 2005 59 68
35. D.R. Plas, and C.B. Thompson Akt activation promotes degradation of tuberin and FOXO3a via the proteasome J. Biol. Chem. 278 2003 12361 12366 (Pubitemid 36800220)
36. C.J. Potter, L.G. Pedraza, and T. Xu Akt regulates growth by directly phosphorylating Tsc2 Nat. Cell Biol. 4 2002 658 665 (Pubitemid 34993701)
37. K. Saito, Y. Araki, K. Kontani, H. Nishina, and T. Katada Novel role of the small GTPase Rheb: its implication in endocytic pathway independent of the activation of mammalian target of rapamycin J. Biochem. 137 2005 423 430 (Pubitemid 40628451)
38. Y. Sancak, C.C. Thoreen, T.R. Peterson, R.A. Lindquist, S.A. Kang, E. Spooner, S.A. Carr, and D.M. Sabatini PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase Mol. Cell 25 2007 903 915 (Pubitemid 46436534)
39. Y. Sancak, T.R. Peterson, Y.D. Shaul, R.A. Lindquist, C.C. Thoreen, L. Bar-Peled, and D.M. Sabatini The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1 Science 320 2008 1496 1501 (Pubitemid 351929429)
40. Y. Sancak, L. Bar-Peled, R. Zoncu, A.L. Markhard, S. Nada, and D.M. Sabatini Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids Cell 141 2010 290 303
41. W. Sun, Y.J. Zhu, Z. Wang, Q. Zhong, F. Gao, J. Lou, W. Gong, and W. Xu Crystal structure of the yeast TSC1 core domain and implications for tuberous sclerosis pathological mutations Nat Commun. 4 2013 2135
42. K. Takahashi, M. Nakagawa, S.G. Young, and S. Yamanaka Differential membrane localization of ERas and Rheb, two Ras-related proteins involved in the phosphatidylinositol 3-kinase/mTOR pathway J. Biol. Chem. 280 2005 32768 32774 (Pubitemid 41368323)
43. L. Wang, C.J. Rhodes, and J.C. Lawrence Jr. Activation of mammalian target of rapamycin (mTOR) by insulin is associated with stimulation of 4EBP1 binding to dimeric mTOR complex 1 J. Biol. Chem. 281 2006 24293 24303 (Pubitemid 44274202)
44. C.K. Yip, K. Murata, T. Walz, D.M. Sabatini, and S.A. Kang Structure of the human mTOR complex I and its implications for rapamycin inhibition Mol. Cell 38 2010 768 774
45. H.H. Zhang, J. Huang, K. Düvel, B. Boback, S. Wu, R.M. Squillace, C.L. Wu, and B.D. Manning Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway PLoS ONE 4 2009 e6189
46. R. Zoncu, L. Bar-Peled, A. Efeyan, S. Wang, Y. Sancak, and D.M. Sabatini mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase Science 334 2011 678 683
47. L.A. Albertti, A.M. Macedo, E. Chiari, N.W. Andrews, and L.O. Andrade Role of host lysosomal associated membrane protein (LAMP) in Trypanosoma cruzi invasion and intracellular development Microbes Infect. 12 2010 784 789
48. Z. Chen, L.C. Trotman, D. Shaffer, H.K. Lin, Z.A. Dotan, M. Niki, J.A. Koutcher, H.I. Scher, T. Ludwig, and W. Gerald et al. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis Nature 436 2005 725 730 (Pubitemid 41117277)
49. A. Romanelli, K.A. Martin, A. Toker, and J. Blenis p70 S6 kinase is regulated by protein kinase Czeta and participates in a phosphoinositide 3-kinase-regulated signalling complex Mol. Cell. Biol. 19 1999 2921 2928 (Pubitemid 29144537)
50. A.R. Tee, B.D. Manning, P.P. Roux, L.C. Cantley, and J. Blenis Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb Curr. Biol. 13 2003 1259 1268 (Pubitemid 36953298)
51. H. Zhang, G. Cicchetti, H. Onda, H.B. Koon, K. Asrican, N. Bajraszewski, F. Vazquez, C.L. Carpenter, and D.J. Kwiatkowski Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR J. Clin. Invest. 112 2003 1223 1233 (Pubitemid 38056299)