Cardiac mTOR complex 2 preserves ventricular function in pressure-overload hypertrophy

Cardiovascular Research

Volumn 109, Issue 1, 2016, Pages 103-114

  Shende, Pankaj ^a   Xu, Lifen ^a   Morandi, Christian ^a   Pentassuglia, Laura ^a   Heim, Philippe ^a   Lebboukh, Sonia ^a   Berthonneche, Corinne ^b   Pedrazzini, Thierry ^b   Kaufmann, Beat A ^a   Hall, Michael N ^c   Rüegg, Markus A ^c   Brink, Marijke ^a  

^a UNIVERSITY HOSPITAL BASEL   (Switzerland)

^b University of Lausanne Medical Center   (Switzerland)

^c UNIVERSITY OF BASEL   (Switzerland)

Author keywords

Heart failure; Hypertrophy; Metabolism; Signal transduction

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; PROTEIN KINASE B; PROTEIN KINASE C BETA; PROTEIN KINASE C DELTA; CARRIER PROTEIN; MULTIPROTEIN COMPLEX; PHOSPHOPROTEIN; PROLINE-RICH AKT SUBSTRATE, 40 KDA PROTEIN, MOUSE; PROTEIN KINASE C; RICTOR PROTEIN, MOUSE; TARGET OF RAPAMYCIN KINASE; TOR COMPLEX 2;

ADULT; AORTA CONSTRICTION; APOPTOSIS; ARTICLE; CONTROLLED STUDY; GENE DELETION; GENE EXPRESSION; HEART FUNCTION; HEART MUSCLE CELL; HEART VENTRICLE FUNCTION; HEART VENTRICLE HYPERTROPHY; HEART WEIGHT; HEMODYNAMIC STRESS; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; ANIMAL; C57BL MOUSE; CARDIAC MUSCLE; CARDIOMEGALY; FIBROSIS; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; PHOSPHORYLATION; PHYSIOLOGY;

ANIMALS; APOPTOSIS; CARDIOMEGALY; CARRIER PROTEINS; FIBROSIS; MALE; MICE; MICE, INBRED C57BL; MULTIPROTEIN COMPLEXES; MYOCARDIUM; PHOSPHOPROTEINS; PHOSPHORYLATION; PROTEIN KINASE C; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; VENTRICULAR FUNCTION;

EID: 84959900835     PISSN: 00086363     EISSN: 17553245     Source Type: Journal    
DOI: 10.1093/cvr/cvv252     Document Type: Article

References (57)

1. Sciarretta S, Volpe M, Sadoshima J. Mammalian target of rapamycin signaling in cardiac physiology and disease. Circ Res 2014; 114: 549-564
2. Dibble CC, Manning BD. Signal integration by mTORC1 coordinates nutrient input with biosynthetic output. Nat Cell Biol 2013; 15: 555-564
3. Song X, Kusakari Y, Xiao CY, Kinsella SD, Rosenberg MA, Scherrer-Crosbie M, Hara K, Rosenzweig A, Matsui T. mTOR attenuates the inflammatory response in cardiomyocytes and prevents cardiac dysfunction in pathological hypertrophy. Am J Physiol Cell Physiol 2010; 299: C1256-C1266
4. Zhang D, Contu R, Latronico MV, Zhang JL, Rizzi R, Catalucci D, Miyamoto S, Huang K, Ceci M, Gu Y, Dalton ND, Peterson KL, Guan KL, Brown JH, Chen J, Sonenberg N, Condorelli G. MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice. J Clin Invest 2010; 120: 2805-2816
5. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell 2006; 124: 471-484
6. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell 2012; 149: 274-293
7. Shende P, Plaisance I, Morandi C, Pellieux C, Berthonneche C, Zorzato F, Krishnan J, Lerch R, Hall MN, Ruegg MA, Pedrazzini T, Brink M. Cardiac raptor ablation impairs adaptive hypertrophy, alters metabolic gene expression, and causes heart failure in mice. Circulation 2011; 123: 1073-1082
8. Oh WJ, Jacinto E. mTOR complex 2 signaling and functions. Cell Cycle 2011; 10: 2305-2316
9. Bentzinger CF, Romanino K, Cloetta D, Lin S, Mascarenhas JB, Oliveri F, Xia J, Casanova E, Costa CF, Brink M, Zorzato F, Hall MN, Ruegg M.A. Skeletal musclespecific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy. Cell Metab 2008; 8: 411-424
10. Kumar A, Harris TE, Keller SR, Choi KM, Magnuson MA, Lawrence JC Jr. Musclespecific deletion of rictor impairs insulin-stimulated glucose transport and enhances basal glycogen synthase activity. Mol Cell Biol 2008; 28: 61-70
11. Cybulski N, Polak P, Auwerx J, Ruegg MA, Hall MN. mTOR complex 2 in adipose tissue negatively controls whole-body growth. Proc Natl Acad Sci USA 2009; 106: 9902-9907
12. Hagiwara A, Cornu M, Cybulski N, Polak P, Betz C, Trapani F, Terracciano L, Heim MH, Ruegg MA, Hall MN. Hepatic mTORC2 activates glycolysis and lipogenesis through Akt, glucokinase, and SREBP1c. Cell Metab 2012; 15: 725-738
13. Thomanetz V, Angliker N, Cloetta D, Lustenberger RM, Schweighauser M, Oliveri F, Suzuki N, Ruegg M.A. Ablation of the mTORC2 component rictor in brain or Purkinje cells affects size and neuron morphology. J Cell Biol 2013; 201: 293-308
14. Huang W, Zhu PJ, Zhang S, Zhou H, Stoica L, Galiano M, Krnjevic K, Roman G, Costa-Mattioli M. mTORC2 controls actin polymerization required for consolidation of long-term memory. Nat Neurosci 2013; 16: 441-448
15. Bercury KK, Dai J, Sachs HH, Ahrendsen JT, Wood TL, Macklin WB. Conditional ablation of raptor or rictor has differential impact on oligodendrocyte differentiation and CNS myelination. J Neurosci 2014; 34: 4466-4480
16. Choo AY, Yoon SO, Kim SG, Roux PP, Blenis J. Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation. Proc Natl Acad Sci USA 2008; 105: 17414-17419
17. Wang X, Yue P, Kim YA, Fu H, Khuri FR, Sun SY. Enhancing mammalian target of rapamycin (mTOR)-targeted cancer therapy by preventing mTOR/raptor inhibition-initiated, mTOR/rictor-independent Akt activation. Cancer Res 2008; 68: 7409-7418
18. Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL, Sabatini DM. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006; 22: 159-168
19. Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, Davis JG, Salmon AB, Richardson A, Ahima RS, Guertin DA, Sabatini DM, Baur JA. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science 2012; 335: 1638-1643
20. Nagata K, Liao R, Eberli FR, Satoh N, Chevalier B, Apstein CS, Suter TM. Early changes in excitation-contraction coupling: transition from compensated hypertrophy to failure in Dahl salt-sensitive rat myocytes. Cardiovasc Res 1998; 37: 467-477
21. Polak P, Cybulski N, Feige JN, Auwerx J, Ruegg MA, Hall MN. Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration. Cell Metab 2008; 8: 399-410
22. Sohal DS, Nghiem M, Crackower MA, Witt SA, Kimball TR, Tymitz KM, Penninger JM, Molkentin JD. Temporally regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein. Circ Res 2001; 89: 20-25
23. Liu Q, Molkentin JD. Protein kinase C alpha as a heart failure therapeutic target. J Mol Cell Cardiol 2011; 51: 474-478
24. Palaniyandi SS, Sun L, Ferreira JC, Mochly-Rosen D. Protein kinase C in heart failure: a therapeutic target?. Cardiovasc Res 2009; 82: 229-239
25. Duquesnes N, Lezoualc'h F, Crozatier B. PKC-delta and PKC-epsilon: foes of the same family or strangers?. J Mol Cell Cardiol 2011; 51: 665-673
26. Guertin DA, Stevens DM, Thoreen CC, Burds AA, Kalaany NY, Moffat J, Brown M, Fitzgerald KJ, Sabatini DM. Ablation in mice of the mTORC components raptor, ricto r, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell 2006; 11: 859-871
27. Sussman MA, Volkers M, Fischer K, Bailey B, Cottage CT, Din S, Gude N, Avitabile D, Alvarez R, Sundararaman B, Quijada P, Mason M, Konstandin MH, Malhowski A, Cheng Z, Khan M, McGregor M. Myocardial AKT: the omnipresent nexus. Physiol Rev 2011; 91: 1023-1070
28. Ikenoue T, Inoki K, Yang Q, Zhou X, Guan KL. Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling. EMBO J 2008; 27: 1919-1931
29. Oh WJ, Wu CC, Kim SJ, Facchinetti V, Julien LA, Finlan M, Roux PP, Su B, Jacinto E. mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide. EMBO J 2010; 29: 3939-3951
30. Alessi DR, James SR, Downes CP, Holmes AB, Gaffney PR, Reese CB, Cohen P. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha. Curr Biol 1997; 7: 261-269
31. Zhu Y, Soto J, Anderson B, Riehle C, Zhang YC, Wende AR, Jones D, McClain DA, Abel ED. Regulation of fatty acid metabolism by mTOR in adult murine hearts occurs independently of changes in PGC-1alpha. Am J Physiol Heart Circ Physiol 2013; 305: H41-H51
32. Garcia-Martinez JM, Alessi DR. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem J 2008; 416: 375-385
33. Brunet A, Park J, Tran H, Hu LS, Hemmings BA, Greenberg ME. Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). Mol Cell Biol 2001; 21: 952-965
34. Aoyama T, Matsui T, Novikov M, Park J, Hemmings B, Rosenzweig A. Serum and glucocorticoid-responsive kinase-1 regulates cardiomyocyte survival and hypertrophic response. Circulation 2005; 111: 1652-1659
35. Song M, Matkovich SJ, Zhang Y, Hammer DJ, Dorn GW II. Combined cardiomyocyte PKCdelta and PKCepsilon gene deletion uncovers their central role in restraining developmental and reactive heart growth. Sci Signal 2015; 8: ra39
36. Volkers M, Konstandin MH, Doroudgar S, Toko H, Quijada P, Din S, Joyo A, Ornelas L, Samse K, Thuerauf DJ, Gude N, Glembotski CC, Sussman M.A. Mechanistic target of rapamycin complex 2 protects the heart from ischemic damage. Circulation 2013; 128: 2132-2144
37. Shimobayashi M, Hall MN. Making new contacts: the mTOR network in metabolism and signalling crosstalk. Nat Rev Mol Cell Biol 2014; 15: 155-162
38. Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 2004; 14: 1296-1302
39. Facchinetti V, Ouyang W, Wei H, Soto N, Lazorchak A, Gould C, Lowry C, Newton AC, Mao Y, Miao RQ, Sessa WC, Qin J, Zhang P, Su B, Jacinto E. The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C. EMBO J 2008; 27: 1932-1943
40. Li W, Zhang J, Bottaro DP, Pierce JH. Identification of serine 643 of protein kinase C-delta as an important autophosphorylation site for its enzymatic activity. J Biol Chem 1997; 272: 24550-24555
41. Parekh D, Ziegler W, Yonezawa K, Hara K, Parker PJ. Mammalian TOR controls one of two kinase pathways acting upon nPKCdelta and nPKCepsilon. J Biol Chem 1999; 274: 34758-34764
42. Basu A, Sridharan S, Persaud S. Regulation of protein kinase C delta downregulation by protein kinase C epsilon and mammalian target of rapamycin complex 2. Cell Signal 2009; 21: 1680-1685
43. Gallegos LL, Newton AC. Spatiotemporal dynamics of lipid signaling: protein kinase C as a paradigm. IUBMB Life 2008; 60: 782-789
44. Freeley M, Kelleher D, Long A. Regulation of protein kinase C function by phosphorylation on conserved and non-conserved sites. Cell Signal 2011; 23: 753-762
45. Liu Q, Chen X, Macdonnell SM, Kranias EG, Lorenz JN, Leitges M, Houser SR, Molkentin JD. Protein kinase C{alpha}, but not PKC{beta} or PKC{gamma}, regulates contractility and heart failure susceptibility: implications for ruboxistaurin as a novel therapeutic approach. Circ Res 2009; 105: 194-200.
46. Cornu M, Albert V, Hall MN. mTOR in aging, metabolism, and cancer. Curr Opin Genet Dev 2013; 23: 53-62
47. Mayr M, Chung YL, Mayr U, McGregor E, Troy H, Baier G, Leitges M, Dunn MJ, Griffiths JR, Xu Q. Loss of PKC-delta alters cardiac metabolism. Am J Physiol Heart Circ Physiol 2004; 287: H937-H945
48. Mayr M, Metzler B, Chung YL, McGregor E, Mayr U, Troy H, Hu Y, Leitges M, Pachinger O, Griffiths JR, Dunn MJ, Xu Q. Ischemic preconditioning exaggerates cardiac damage in PKC-delta null mice. Am J Physiol Heart Circ Physiol 2004; 287: H946-H956
49. Godel M, Hartleben B, Herbach N, Liu S, Zschiedrich S, Lu S, Debreczeni-Mor A, Lindenmeyer MT, Rastaldi MP, Hartleben G, Wiech T, Fornoni A, Nelson RG, Kretzler M, Wanke R, Pavenstadt H, Kerjaschki D, Cohen CD, Hall MN, Ruegg MA, Inoki K, Walz G, Huber TB. Role of mTOR in podocyte function and diabetic nephropathy in humans and mice. J Clin Invest 2011; 121: 2197-2209.
50. Hietakangas V, Cohen SM. Re-evaluating AKT regulation: role of TOR complex 2 in tissue growth. Genes Dev 2007; 21: 632-637
51. Shiojima I, Yefremashvili M, Luo Z, Kureishi Y, Takahashi A, Tao J, Rosenzweig A, Kahn CR, Abel ED, Walsh K. Akt signaling mediates postnatal heart growth in response to insulin and nutritional status. J Biol Chem 2002; 277: 37670-37677
52. Naga Prasad SV, Esposito G, Mao L, Koch WJ, Rockman HA. Gbetagamma-dependent phosphoinositide 3-kinase activation in hearts with in vivo pressure overload hypertrophy. J Biol Chem 2000; 275: 4693-4698
53. Shioi T, McMullen JR, Kang PM, Douglas PS, Obata T, Franke TF, Cantley LC, Izumo S. Akt/protein kinase B promotes organ growth in transgenic mice. Mol Cell Biol 2002; 22: 2799-2809
54. Condorelli G, Drusco A, Stassi G, Bellacosa A, Roncarati R, Iaccarino G, Russo MA, Gu Y, Dalton N, Chung C, Latronico MV, Napoli C, Sadoshima J, Croce CM, Ross J Jr. Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice. Proc Natl Acad Sci USA 2002; 99: 12333-12338
55. Moschella PC, Rao VU, McDermott PJ, Kuppuswamy D. Regulation of mTOR and S6K1 activation by the nPKC isoforms, PKCepsilon and PKCdelta, in adult cardiac muscle cells. J Mol Cell Cardiol 2007; 43: 754-766
56. Wang L, Rolfe M, Proud CG. Ca(2+)-independent protein kinase C activity is required for alpha1-adrenergic-receptor-mediated regulation of ribosomal protein S6 kinases in adult cardiomyocytes. Biochem J 2003; 373: 603-611
57. McMullen JR, Shioi T, Zhang L, Tarnavski O, Sherwood MC, Dorfman AL, Longnus S, Pende M, Martin KA, Blenis J, Thomas G, Izumo S. Deletion of ribosomal S6 kinases does not attenuate pathological, physiological, or insulin-like growth factor 1 receptorphosphoinositide 3-kinase-induced cardiac hypertrophy. Mol Cell Biol 2004; 24: 6231-6240