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2014 | 1 | 1 |

Article title

Cellular metabolism and lysosomal mTOR
signaling

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EN

Abstracts

EN
Over the last few years extensive studies have
linked the activity of mTORC1 to lysosomal function. These
observations propose an intriguing integration of cellular
catabolism, sustained by lysosomes, with anabolic
processes, largely controlled by mTORC1. Interestingly,
lysosomal function directly affects mTORC1 activity and
is regulated by ZKSCAN3 and TFEB, two transcription
factors and substrates of mTORC1. Thus, the lysosomal
mTOR signaling complex represents a hub of cellular
energy metabolism, and its dysregulation may lead to a
number of human diseases. Here, we discuss the recent
developments and highlight the open questions in this
growing field.

Keywords

Publisher

Year

Volume

1

Issue

1

Physical description

Dates

received
24 - 11 - 2014
accepted
29 - 12 - 2014
online
30 - 1 - 2015

Contributors

  • Federated Department
    of Biological Sciences, Rutgers University/New Jersey Institute of
    Technology, Newark, NJ 07102
  • Federated Department
    of Biological Sciences, Rutgers University/New Jersey Institute of
    Technology, Newark, NJ 07102
  • Federated Department
    of Biological Sciences, Rutgers University/New Jersey Institute of
    Technology, Newark, NJ 07102

References

  • [1] Laplante M, Sabatini DM: MTOR signaling in growth control anddisease. Cell 2012:274–293.[Crossref]
  • [2] Settembre C, De Cegli R, Mansueto G, Saha PK, VetriniF, Visvikis O, Huynh T, Carissimo A, Palmer D, Klisch TJ,Wollenberg AC, Di Bernardo D, Chan L, Irazoqui JE, Ballabio A:TFEB controls cellular lipid metabolism through a starvationinducedautoregulatory loop. Nat Cell Biol 2013, 15:647–58.[Crossref]
  • [3] Settembre C, Fraldi A, Medina DL, Ballabio A: Signals from thelysosome: a control centre for cellular clearance and energymetabolism. Nat Rev Mol Cell Biol 2013, 14:283–96.[Crossref]
  • [4] Bagshaw RD, Mahuran DJ, Callahan JW: Lysosomal membraneproteomics and biogenesis of lysosomes. Mol Neurobiol 2005,32:27–41.[Crossref]
  • [5] Sridhar S, Patel B, Aphkhazava D, Macian F, SantambrogioL, Shields D, Cuervo AM: The lipid kinase PI4KIIIβ preserveslysosomal identity. EMBO J 2013, 32:324–39.
  • [6] Schulze H, Kolter T, Sandhoff K: Principles of lysosomalmembrane degradation. Cellular topology and biochemistry oflysosomal lipid degradation. Biochimica et Biophysica Acta -Molecular Cell Research 2009:674–683.[Crossref]
  • [7] Saftig P, Klumperman J: Lysosome biogenesis and lysosomalmembrane proteins: trafficking meets function. Nat Rev MolCell Biol 2009, 10:623–635.[Crossref]
  • [8] Kaushik S, Cuervo AM: Chaperone-mediated autophagy: Aunique way to enter the lysosome world. Trends in Cell Biology2012:407–417.[Crossref]
  • [9] Andrejewski N, Punnonen EL, Guhde G, Tanaka Y, Lüllmann-Rauch R, Hartmann D, Von Figura K, Saftig P: Normal lysosomalmorphology and function in LAMP-1-deficient mice. J Biol Chem1999, 274:12692–12701.
  • [10] Cafferkey R, Young PR, McLaughlin MM, Bergsma DJ, Koltin Y,Sathe GM, Faucette L, Eng WK, Johnson RK, Livi GP: Dominantmissense mutations in a novel yeast protein related tomammalian phosphatidylinositol 3-kinase and VPS34 abrogaterapamycin cytotoxicity. Mol Cell Biol 1993, 13:6012–6023.[Crossref]
  • [11] Kunz J, Henriquez R, Schneider U, Deuter-Reinhard M,Movva NR, Hall MN: Target of rapamycin in yeast, TOR2, is anessential phosphatidylinositol kinase homolog required for G1progression. Cell 1993, 73:585–596.[Crossref]
  • [12] Wullschleger S, Loewith R, Hall MN: TOR signaling in growthand metabolism. Cell 2006:471–484.[Crossref]
  • [13] Loewith R, Hall MN: Target of rapamycin (TOR) in nutrientsignaling and growth control. Genetics 2011:1177–1201.[Crossref]
  • [14] Jacinto E, Facchinetti V, Liu D, Soto N, Wei S, Jung SY, Huang Q,Qin J, Su B: SIN1/MIP1 Maintains rictor-mTOR Complex Integrityand Regulates Akt Phosphorylation and Substrate Specificity.Cell 2006, 127:125–137.[Crossref]
  • [15] Nobukuni T, Joaquin M, Roccio M, Dann SG, Kim SY, Gulati P,Byfield MP, Backer JM, Natt F, Bos JL, Zwartkruis FJT, Thomas G:Amino acids mediate mTOR/raptor signaling through activationof class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad SciU S A 2005, 102:14238–14243.[Crossref]
  • [16] Tato I, Bartrons R, Ventura F, Rosa JL: Amino acids activatemammalian target of rapamycin complex 2 (mTORC2) via PI3K/Akt signaling. J Biol Chem 2011, 286:6128–6142.
  • [17] Frias MA, Thoreen CC, Jaffe JD, Schroder W, Sculley T, Carr SA,Sabatini DM: mSin1 Is Necessary for Akt/PKB Phosphorylation,and Its Isoforms Define Three Distinct mTORC2s. Curr Biol2006, 16:1865–1870.[Crossref]
  • [18] Zinzalla V, Stracka D, Oppliger W, Hall MN: Activation ofmTORC2 by association with the ribosome. Cell 2011,144:757–768.
  • [19] García-Martínez JM, Alessi DR: mTOR complex 2 (mTORC2)controls hydrophobic motif phosphorylation and activation ofserum- and glucocorticoid-induced protein kinase 1 (SGK1).Biochem J 2008, 416:375–385.
  • [20] Guertin DA, Stevens DM, Thoreen CC, Burds AA, Kalaany NY,Moffat J, Brown M, Fitzgerald KJ, Sabatini DM: Ablation in Miceof the mTORC Components raptor, rictor, or mLST8 Reveals thatmTORC2 Is Required for Signaling to Akt-FOXO and PKC, but NotS6K1. Dev Cell 2006, 11:859–871.[Crossref]
  • [21] Dos DS, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM: Rictor, a novel bindingpartner of mTOR, defines a rapamycin-insensitive and raptorindependentpathway that regulates the cytoskeleton. Curr Biol2004, 14:1296–1302.
  • [22] Sarbassov DD, Guertin DA, Ali SM, Sabatini DM: Phosphorylationand regulation of Akt/PKB by the rictor-mTOR complex.Science 2005, 307:1098–1101.
  • [23] Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang S a.,Kuehl WM, Gray NS, Sabatini DM: DEPTOR Is an mTOR InhibitorFrequently Overexpressed in Multiple Myeloma Cells andRequired for Their Survival. Cell 2009, 137:873–886.
  • [24] Jacinto E, Loewith R, Schmidt A, Lin S, Rüegg MA, Hall A, HallMN: Mammalian TOR complex 2 controls the actin cytoskeletonand is rapamycin insensitive. Nat Cell Biol 2004, 6:1122–1128.[Crossref]
  • [25] Kim DH, Sarbassov DD, Ali SM, Latek RR, Guntur KVP,Erdjument-Bromage H, Tempst P, Sabatini DM: GbL, a positiveregulator of the rapamycin-sensitive pathway required for thenutrient-sensitive interaction between raptor and mTOR. MolCell 2003, 11:895–904.[Crossref]
  • [26] Kaizuka T, Hara T, Oshiro N, Kikkawa U, Yonezawa K, TakehanaK, Iemura SI, Natsume T, Mizushima N: Tti1 and Tel2 are criticalfactors in mammalian target of rapamycin complex assembly. JBiol Chem 2010, 285:20109–20116.
  • [27] Sancak Y, Thoreen CC, Peterson TR, Lindquist RA, Kang SA,Spooner E, Carr SA, Sabatini DM: PRAS40 Is an Insulin-Regulated Inhibitor of the mTORC1 Protein Kinase. Mol Cell2007, 25:903–915.
  • [28] Thedieck K, Holzwarth B, Prentzell MT, Boehlke C, KläsenerK, Ruf S, Sonntag AG, Maerz L, Grellscheid SN, KremmerE, Nitschke R, Kuehn EW, Jonker JW, Groen AK, Reth M, HallMN, Baumeister R: Inhibition of mTORC1 by astrin and stressgranules prevents apoptosis in cancer cells. Cell 2013,154:859–874.
  • [29] Vander Haar E, Lee S-I, Bandhakavi S, Griffin TJ, Kim D-H:Insulin signalling to mTOR mediated by the Akt/PKB substratePRAS40. Nat Cell Biol 2007, 9:316–323.
  • [30] Wang L, Harris TE, Roth RA, Lawrence JC: PRAS40 regulatesmTORC1 kinase activity by functioning as a direct inhibitor ofsubstrate binding. J Biol Chem 2007, 282:20036–20044.
  • [31] Hara K, Maruki Y, Long X, Yoshino K ichi, Oshiro N, Hidayat S,Tokunaga C, Avruch J, Yonezawa K: Raptor, a binding partnerof target of rapamycin (TOR), mediates TOR action. Cell 2002,110:177–189.[Crossref]
  • [32] Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM: mTOR interacts with raptorto form a nutrient-sensitive complex that signals to the cellgrowth machinery. Cell 2002, 110:163–175.[Crossref]
  • [33] Pearce LR, Huang X, Boudeau J, Pawłowski R, Wullschleger S,Deak M, Ibrahim AFM, Gourlay R, Magnuson MA, Alessi DR:Identification of Protor as a novel Rictor-binding component ofmTOR complex-2. Biochem J 2007, 405:513–522.
  • [34] Pearce LR, Sommer EM, Sakamoto K, Wullschleger S, Alessi DR:Protor-1 is required for efficient mTORC2-mediated activation ofSGK1 in the kidney. Biochem J 2011, 436:169–179.
  • [35] Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, BagleyAF, Markhard AL, Sabatini DM: Prolonged Rapamycin TreatmentInhibits mTORC2 Assembly and Akt/PKB. Mol Cell 2006,22:159–168.[Crossref]
  • [36] Settembre C, Zoncu R, Medina DL, Vetrini F, Erdin S, ErdinS, Huynh T, Ferron M, Karsenty G, Vellard MC, Facchinetti V:A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB open. EMBO J 2012,31:1095–1108.[Crossref]
  • [37] Kim E, Goraksha-Hicks P, Li L, Neufeld TP, Guan K-L: Regulationof TORC1 by Rag GTPases in nutrient response. Nat Cell Biol2008, 10:935–945.[Crossref]
  • [38] Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC,Bar-Peled L, Sabatini DM: The Rag GTPases bind raptor andmediate amino acid signaling to mTORC1. Science 2008,320:1496–1501.
  • [39] Inoki K, Li Y, Xu T, Guan KL: Rheb GTpase is a direct target ofTSC2 GAP activity and regulates mTOR signaling. Genes Dev2003, 17:1829–1834.[Crossref]
  • [40] Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J: TuberousSclerosis Complex gene products, Tuberin and Hamartin,control mTOR signaling by acting as a GTPase-activatingprotein complex toward Rheb. Curr Biol 2003, 13:1259–1268.[Crossref]
  • [41] Ohkuma S, Moriyama Y, Takano T: Identification andcharacterization of a proton pump on lysosomes by fluoresceinisothiocyanate-dextran fluorescence. Proc Natl Acad Sci U S A1982, 79:2758–2762.[Crossref]
  • [42] Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, SabatiniDM: Ragulator-rag complex targets mTORC1 to the lysosomalsurface and is necessary for its activation by amino acids. Cell2010, 141:290–303.
  • [43] Cang C, Zhou Y, Navarro B, Seo YJ, Aranda K, Shi L, Battaglia-Hsu S, Nissim I, Clapham DE, Ren D: MTOR regulates lysosomalATP-sensitive two-pore Na+ channels to adapt to metabolicstate. Cell 2013, 152:778–790.
  • [44] Sardiello M, Palmieri M, di Ronza A, Medina DL, Valenza M,Gennarino VA, Di Malta C, Donaudy F, Embrione V, PolishchukRS, Banfi S, Parenti G, Cattaneo E, Ballabio A: A gene networkregulating lysosomal biogenesis and function. Science 2009,325:473–477.
  • [45] Puertollano R: mTOR and lysosome regulation. F1000Prime Rep2014, 6(July):52.
  • [46] Budanov A V., Karin M: p53 Target Genes Sestrin1 and Sestrin2Connect Genotoxic Stress and mTOR Signaling. Cell 2008,134:451–460.
  • [47] Martina J a., Chen Y, Gucek M, Puertollano R: MTORC1 functionsas a transcriptional regulator of autophagy by preventingnuclear transport of TFEB. Autophagy 2012, 8:903–914.[Crossref]
  • [48] Chauhan S, Goodwin JG, Chauhan S, Manyam G, Wang J, KamatAM, Boyd DD: ZKSCAN3 Is a Master Transcriptional Repressorof Autophagy. Mol Cell 2013, 50:16–28.[Crossref]
  • [49] Urrutia R: KRAB-containing zinc-finger repressor proteins.Genome Biol 2003, 4:231.[Crossref]
  • [50] Füllgrabe J, Klionsky DJ, Joseph B: The return of the nucleus:transcriptional and epigenetic control of autophagy. Nat RevMol Cell Biol 2014, 15:65–74.
  • [51] Inoki K, Zhu T, Guan K-L: TSC2 mediates cellular energyresponse to control cell growth and survival. Cell 2003,115:577–590.
  • [52] Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP:Phosphorylation and functional inactivation of TSC2 by Erk:Implications for tuberous sclerosis and cancer pathogenesis.Cell 2005, 121:179–193.[Crossref]
  • [53] Potter CJ, Pedraza LG, Xu T: Akt regulates growth by directlyphosphorylating Tsc2. Nat Cell Biol 2002, 4:658–665.[Crossref]
  • [54] Inoki K, Li Y, Zhu T, Wu J, Guan K-L: TSC2 is phosphorylated andinhibited by Akt and suppresses mTOR signalling. Nat Cell Biol2002, 4:648–657.[Crossref]
  • [55] Sato T, Nakashima A, Guo L, Tamanoi F: Specific activationof mTORC1 by Rheb G-protein in vitro involves enhancedrecruitment of its substrate protein. J Biol Chem 2009,284:12783–12791.
  • [56] Manning BD, Tee AR, Logsdon MN, Blenis J, Cantley LC: Identificationof the tuberous sclerosis complex-2 tumor suppressorgene product tuberin as a target of the phosphoinositide3-kinase/Akt pathway. Mol Cell 2002, 10:151–162.
  • [57] Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J: Tumor-promotingphorbol esters and activated Ras inactivate the tuberoussclerosis tumor suppressor complex via p90 ribosomal S6kinase. Proc Natl Acad Sci U S A 2004, 101:13489–13494.[Crossref]
  • [58] Thedieck K, Polak P, Kim ML, Molle KD, Cohen A, Jenö P,Arrieumerlou C, Hall MN: PRAS40 and PRR5-like protein arenew mTOR interactors that regulate apoptosis. PLoS One 2007,2.
  • [59] Wang Z, Liu S, Kakizaki M, Hirose Y, Ishikawa Y, Funato H,Yanagisawa M, Yu Y, Liu Q: Orexin/Hypocretin Activates mTORComplex 1 (mTORC1) via an Erk/Akt-independent and CalciumstimulatedLysosome v-ATPase Pathway. J Biol Chem 2014,289:31950–9.
  • [60] Clevers H, Nusse R: Wnt/Beta-catenin signaling and disease.Cell 2012:1192–1205.[Crossref]
  • [61] Taelman VF, Dobrowolski R, Plouhinec JL, Fuentealba LC,Vorwald PP, Gumper I, Sabatini DD, De Robertis EM: Wntsignaling requires sequestration of Glycogen Synthase Kinase3 inside multivesicular endosomes. Cell 2010, 143:1136–1148.
  • [62] Dobrowolski R, De Robertis EM: Endocytic control of growthfactor signalling: multivesicular bodies as signallingorganelles. Nature Reviews Molecular Cell Biology 2011.
  • [63] Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, YangQ, Bennett C, Harada Y, Stankunas K, Wang C yu, He X,MacDougald OA, You M, Williams BO, Guan KL: TSC2 IntegratesWnt and Energy Signals via a Coordinated Phosphorylationby AMPK and GSK3 to Regulate Cell Growth. Cell 2006,126:955–968.[Crossref]
  • [64] Dobrowolski R, Vick P, Ploper D, Gumper I, Snitkin H, SabatiniDD, De Robertis EM: Presenilin Deficiency or LysosomalInhibition Enhances Wnt Signaling through Relocalization ofGSK3 to the Late-Endosomal Compartment. Cell Rep 2012,2:1316–1328.[Crossref]
  • [65] Lee S, Shea TB: Regulation of tau proteolysis by phosphatases.Brain Res 2013, 1495:30–36.
  • [66] Morita T, Sobuě K: Specification of neuronal polarity regulatedby local translation of CRMP2 and tau via the mTOR-p70S6Kpathway. J Biol Chem 2009, 284:27734–27745.
  • [67] Lee DF, Kuo HP, Chen C Te, Hsu JM, Chou CK, Wei Y, Sun HL,Li LY, Ping B, Huang WC, He X, Hung JY, Lai CC, Ding Q, Su JL,Yang JY, Sahin AA, Hortobagyi GN, Tsai FJ, Tsai CH, Hung MC:IKKβ Suppression of TSC1 Links Inflammation and TumorAngiogenesis via the mTOR Pathway. Cell 2007, 130:440–455.
  • [68] Tracey KJ, Cerami A: Tumor necrosis factor: a pleiotropiccytokine and therapeutic target. Annu Rev Med 1994,45:491–503.[Crossref]
  • [69] Kawasaki H, Onuki R, Suyama E, Taira K: Identification of genesthat function in the TNF-alpha-mediated apoptotic pathway 2002, 20:376–380.
  • [70] Dan HC, Baldwin AS: Differential involvement of IkappaBkinases alpha and beta in cytokine- and insulin-inducedmammalian target of rapamycin activation determined by Akt. JImmunol 2008, 180:7582–9.[Crossref]
  • [71] Ozes ON, Akca H, Mayo LD, Gustin JA, Maehama T, DixonJE, Donner DB: A phosphatidylinositol 3-kinase/Akt/mTORpathway mediates and PTEN antagonizes tumor necrosisfactor inhibition of insulin signaling through insulin receptorsubstrate-1. Proc Natl Acad Sci U S A 2001, 98:4640–5.[Crossref]
  • [72] Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A,Vasquez DS, Turk BE, Shaw RJ: AMPK Phosphorylation of RaptorMediates a Metabolic Checkpoint. Mol Cell 2008, 30:214–226.[Crossref]
  • [73] Stambolic V, MacPherson D, Sas D, Lin Y, Snow B, Jang Y,Benchimol S, Mak TW: Regulation of PTEN transcription by p53.Mol Cell 2001, 8:317–325.[Crossref]
  • [74] Feng Z, Zhang H, Levine AJ, Jin S: The coordinate regulation ofthe p53 and mTOR pathways in cells. Proc Natl Acad Sci U S A2005, 102:8204–8209.[Crossref]
  • [75] Ma XM, Blenis J: Molecular mechanisms of mTOR-mediatedtranslational control. Nat Rev Mol Cell Biol 2009, 10:307–318.[Crossref]
  • [76] Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS,Sabatini DM: A unifying model for mTORC1-mediated regulationof mRNA translation. Nature 2012, 485:109–13.
  • [77] Yu L, McPhee CK, Zheng L, Mardones G a, Rong Y, Peng J, MiN, Zhao Y, Liu Z, Wan F, Hailey DW, Oorschot V, KlumpermanJ, Baehrecke EH, Lenardo MJ: Termination of autophagy andreformation of lysosomes regulated by mTOR. Nature 2010,465:942–946.
  • [78] Porstmann T, Santos CR, Griffiths B, Cully M, Wu M, Leevers S,Griffiths JR, Chung YL, Schulze A: SREBP Activity Is Regulatedby mTORC1 and Contributes to Akt-Dependent Cell Growth. CellMetab 2008, 8:224–236.[Crossref]
  • [79] Wang BT, Ducker GS, Barczak AJ, Barbeau R, Erle DJ, ShokatKM: The mammalian target of rapamycin regulates cholesterolbiosynthetic gene expression and exhibits a rapamycinresistanttranscriptional profile. Proc Natl Acad Sci U S A 2011,108:15201–15206.[Crossref]
  • [80] Li S, Brown MS, Goldstein JL: Bifurcation of insulin signalingpathway in rat liver: mTORC1 required for stimulation oflipogenesis, but not inhibition of gluconeogenesis. Proc NatlAcad Sci U S A 2010, 107:3441–3446.[Crossref]
  • [81] Bar-Peled L, Sabatini DM: Regulation of mTORC1 by aminoacids. Trends in Cell Biology 2014:400–406.
  • [82] Zoncu R, Bar-Peled L, Efeyan A, Wang S, Sancak Y, Sabatini DM:mTORC1 Senses Lysosomal Amino Acids Through an Inside-OutMechanism That Requires the Vacuolar H+-ATPase. Science2011:678–683.[Crossref]
  • [83] Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, NyfelerB, Yang H, Hild M, Kung C, Wilson C, Myer VE, MacKeiganJP, Porter JA, Wang YK, Cantley LC, Finan PM, Murphy LO:Bidirectional Transport of Amino Acids Regulates mTOR andAutophagy. Cell 2009, 136:521–534.
  • [84] Smith EM, Finn SG, Tee AR, Brownei GJ, Proud CG: The tuberoussclerosis protein TSC2 is not required for the regulation of themammalian target of rapamycin by amino acids and certaincellular stresses. J Biol Chem 2005, 280:18717–18727.
  • [85] Jakubowski H: Quality control in tRNA charging. Wiley InterdisciplinaryReviews: RNA 2012:295–310.
  • [86] Han JM, Jeong SJ, Park MC, Kim G, Kwon NH, Kim HK, Ha SH,Ryu SH, Kim S: Leucyl-tRNA synthetase is an intracellularleucine sensor for the mTORC1-signaling pathway. Cell 2012,149:410–424.
  • [87] Tsun ZY, Bar-Peled L, Chantranupong L, Zoncu R, Wang T, KimC, Spooner E, Sabatini D: The folliculin tumor suppressor is aGAP for the RagC/D GTPases that signal amino acid levels tomTORC1. Mol Cell 2013, 52:495–505.[Crossref]
  • [88] Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, OttinaK a, Grabiner BC, Spear ED, Carter SL, Meyerson M, SabatiniDM: A Tumor suppressor complex with GAP activity for the RagGTPases that signal amino acid sufficiency to mTORC1. Science2013, 340:1100–6.
  • [89] Lerman MI, Minna JD: The 630-kb lung cancer homozygousdeletion region on human chromosome 3p21.3: Identificationand evaluation of the resident candidate tumor suppressorgenes. Cancer Res 2000, 60:6116–6133.
  • [90] Li J, Wang F, Haraldson K, Protopopov A, Duh FM, Geil L, KuzminI, Minna JD, Stanbridge E, Braga E, Kashuba VI, Klein G, LermanMI, Zabarovsky ER: Functional characterization of the candidatetumor suppressor gene NPRL2/G21 located in 3p21.3C. CancerRes 2004, 64:6438–6443.[Crossref]
  • [91] Tzer JS, Ichimura K, Liu L, Tingby O, Pearson DM, Collins VP:Complex chromosome 22 rearrangements in astrocytic tumorsidentified using microsatellite and chromosome 22 tile patharray analysis. Genes Chromosom Cancer 2005, 43:181–193.
  • [92. Peng M, Yin N, Li MO: Sestrins Function as Guanine NucleotideDissociation Inhibitors for Rag GTPases to Control mTORC1Signaling. Cell 2014, 159:122–133.
  • [93] Chantranupong L, Wolfson RL, Orozco JM, Saxton RA, ScariaSM, Bar-Peled L, Spooner E, Isasa M, Gygi SP, Sabatini DM:The Sestrins Interact with GATOR2 to Negatively Regulate theAmino-Acid-Sensing Pathway Upstream of mTORC1. Cell Rep2014, 9:1–8.[Crossref]
  • [94] Betz C, Hall MN: Where is mTOR and what is it doing there?. JCell Biol 2013, 203:563–574.
  • [95] Kim JE, Chen J: Cytoplasmic-nuclear shuttling ofFKBP12-rapamycin-associated protein is involved in rapamycinsensitivesignaling and translation initiation. Proc Natl Acad SciU S A 2000, 97:14340–14345.[Crossref]
  • [96] Schieke SM, Phillips D, McCoy JP, Aponte AM, Shen R-F, BalabanRS, Finkel T: The mammalian target of rapamycin (mTOR)pathway regulates mitochondrial oxygen consumption andoxidative capacity. J Biol Chem 2006, 281:27643–27652.
  • [97] Yang TTC, Yu RYL, Agadir A, Gao G-J, Campos-Gonzalez R,Tournier C, Chow C-W: Integration of protein kinases mTORand extracellular signal-regulated kinase 5 in regulatingnucleocytoplasmic localization of NFATc4. Mol Cell Biol 2008,28:3489–3501.[Crossref]
  • [98] Ramanathan A, Schreiber SL: Direct control of mitochondrialfunction by mTOR. Proc Natl Acad Sci U S A 2009, 106:22229–22232.[Crossref]
  • [99] Takahara T, Maeda T: Transient Sequestration of TORC1 intoStress Granules during Heat Stress. Mol Cell 2012, 47:242–252.
  • [100] Wippich F, Bodenmiller B, Trajkovska MG, Wanka S, AebersoldR, Pelkmans L: Dual specificity kinase DYRK3 couples stressgranule condensation/dissolution to mTORC1 signaling. Cell2013, 152:791–805.
  • [101] Platt FM, Boland B, van der Spoel AC: Lysosomal storagedisorders: The cellular impact of lysosomal dysfunction. J CellBiol 2012, 199:723–734.
  • [102] Suzuki K, Terry RD: Fine structural localization of acidphosphatase in senile plaques in Alzheimer’s preseniledementia. Acta Neuropathol 1967, 8:276–84.[Crossref]
  • [103] Gouras GK, Tsai J, Naslund J, Vincent B, Edgar M, Checler F,Greenfield JP, Haroutunian V, Buxbaum JD, Xu H, GreengardP, Relkin NR: Intraneuronal Abeta42 accumulation in humanbrain. Am J Pathol 2000, 156:15–20.
  • [104] Takahashi RH, Milner TA, Li F, Nam EE, Edgar MA, YamaguchiH, Beal MF, Xu H, Greengard P, Gouras GK: IntraneuronalAlzheimer abeta42 accumulates in multivesicular bodiesand is associated with synaptic pathology. Am J Pathol 2002,161:1869–1879.
  • [105] Rajendran L, Honsho M, Zahn TR, Keller P, Geiger KD, VerkadeP, Simons K: Alzheimer’s disease beta-amyloid peptides arereleased in association with exosomes. Proc Natl Acad Sci U SA 2006, 103:11172–11177.[Crossref]
  • [106] Vella LJ, Sharples RA, Nisbet RM, Cappai R, Hill AF: The roleof exosomes in the processing of proteins associated withneurodegenerative diseases. In European Biophysics Journal.Volume 37; 2008:323–332.[Crossref]
  • [107] Nixon RA, Wegiel J, Kumar A, Yu WH, Peterhoff C, Cataldo A,Cuervo AM: Extensive involvement of autophagy in Alzheimerdisease: an immuno-electron microscopy study. J NeuropatholExp Neurol 2005, 64:113–122.[Crossref]
  • [108] Cataldo AM, Barnett JL, Pieroni C, Nixon RA: Increasedneuronal endocytosis and protease delivery to earlyendosomes in sporadic Alzheimer’s disease: neuropathologicevidence for a mechanism of increased beta-amyloidogenesis.J Neurosci 1997, 17:6142–6151.
  • [109] Nixon RA, Yang DS: Autophagy failure in Alzheimer’sdisease-locating the primary defect. Neurobiology of Disease2011:38–45.[Crossref]
  • [110] Nixon R: The role of autophagy in neurodegenerative disease.Nat Med 2013, 19:983–997.[Crossref]
  • [111] Rao M V., McBrayer MK, Campbell J, Kumar A, Hashim A,Sershen H, Stavrides PH, Ohno M, Hutton M, Nixon RA:Specific Calpain Inhibition by Calpastatin Prevents Tauopathyand Neurodegeneration and Restores Normal Lifespan in TauP301L Mice. J Neurosci 2014, 34:9222–9234.[Crossref]
  • [112] Polito VA, Li H, Martini-Stoica H, Wang B, Yang L, Xu Y,Swartzlander DB, Palmieri M, di Ronza A, Lee VM-Y, SardielloM, Ballabio A, Zheng H: Selective clearance of aberrant tauproteins and rescue of neurotoxicity by transcription factorEB. EMBO Mol Med 2014, 6:1142–60.[Crossref]
  • [113] Zaytseva YY, Valentino JD, Gulhati P, Mark Evers B: MTORinhibitors in cancer therapy. Cancer Letters 2012:1–7.[Crossref]
  • [114] Wong M: Mammalian target of rapamycin (mTOR) pathways inneurological diseases. Biomed J 2012, 36:40–50.

Document Type

Publication order reference

Identifiers

YADDA identifier

bwmeta1.element.-psjd-doi-10_1515_cdth-2015-0001
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