Mammalian target of rapamycin and Rictor control neutrophil chemotaxis by regulating Rac/Cdc42 activity and the actin cytoskeleton

Molecular Biology of the Cell

Volumn 24, Issue 21, 2013, Pages 3369-3380

  He, Yuan ^a   Li, Dong ^a   Cook, Sara L ^a   Yoon, Mee Sup ^a   Kapoor, Ashish ^b   Rao, Christopher V ^b   Kenis, Paul J A ^b   Chen, Jie ^a,b   Wang, Fei ^a,b  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^b UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; PROTEIN CDC42; PROTEIN KINASE B; RAC PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; RICTOR PROTEIN; UNCLASSIFIED DRUG;

ACTIN FILAMENT; ACTIN POLYMERIZATION; ARTICLE; CELL DIFFERENTIATION; CELL MIGRATION; CELL POLARITY; CELL STIMULATION; CONTROLLED STUDY; HUMAN; HUMAN CELL; NEUTROPHIL CHEMOTAXIS; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION;

ACTIN CYTOSKELETON; BLOTTING, WESTERN; CARRIER PROTEINS; CDC42 GTP-BINDING PROTEIN; CELL LINE, TUMOR; CELLS, CULTURED; CHEMOTAXIS, LEUKOCYTE; FLUORESCENT ANTIBODY TECHNIQUE; HL-60 CELLS; HUMANS; MULTIPROTEIN COMPLEXES; N-FORMYLMETHIONINE LEUCYL-PHENYLALANINE; NEUTROPHILS; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-AKT; RAC GTP-BINDING PROTEINS; RNA INTERFERENCE; SIROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 84887072931     PISSN: 10591524     EISSN: 19394586     Source Type: Journal    
DOI: 10.1091/mbc.E13-07-0405     Document Type: Article

References (77)

1. Agarwal NK, Chen CH, Cho H, Boulbes D.R., Spooner E., Sarbassov D.D. (2013). Rictor regulates cell migration by suppressing RhoGDI2. Oncogene 32, 2521-2526.
2. Alessi DR, James SR, Downes C.P., Holmes AB, Gaffney PR, Reese CB, Cohen P. (1997). Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha. Curr Biol 7, 261-269. (Pubitemid 27176852)
3. Andrew N, Insall R.H. (2007). Chemotaxis in shallow gradients is mediated independently of PtdIns 3-kinase by biased choices between random protrusions. Nat Cell Biol 9, 193-200. (Pubitemid 46420862)
4. Barnett SF et al. (2005). Identification and characterization of pleckstrinhomology-domain-dependent and isoenzyme-specific Akt inhibitors. Biochem J 385, 399-408. (Pubitemid 40165072)
5. Bayle JH, Grimley JS, Stankunas K, Gestwicki J.E., Wandless TJ, Crabtree G.R. (2006). Rapamycin analogs with differential binding specificity permit orthogonal control of protein activity. Chem Biol 13, 99-107. (Pubitemid 43099928)
6. Belham C, Wu S, Avruch J. (1999). Intracellular signalling: PDK1 - a kinase at the hub of things. Curr Biol 9, R93-R96. (Pubitemid 29087534)
7. Benard V, Bohl B P, Bokoch G.M. (1999). Characterization of rac and cdc42 activation in chemoattractant-stimulated human neutrophils using a novel assay for active GTPases. J Biol Chem 274, 13198-13204.
8. Bhaskar PT, Hay N. (2007). The two TORCs and Akt. Dev Cell 12, 487-502. (Pubitemid 46523652)
9. Bodin S, Welch M.D. (2005). Plasma membrane organization is essential for balancing competing pseudopod- and uropod-promoting signals during neutrophil polarization and migration. Mol Biol Cell 16, 5773-5783. (Pubitemid 41752225)
10. Bourne HR, Weiner O. (2002). A chemical compass. Nature 419, 21. (Pubitemid 34987854)
11. Cai H, Das S, Kamimura Y., Long Y, Parent CA, Devreotes P.N. (2010). Ras-mediated activation of the TORC2-PKB pathway is critical for chemotaxis. J Cell Biol 190, 233-245.
12. Chen L, Iijima M, Tang M., Landree MA, Huang YE, Xiong Y, Iglesias P.A., Devreotes P.N. (2007). PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxis. Dev Cell 12, 603-614. (Pubitemid 46523645)
13. Colvin RA, Campanella GS, Manice L.A., Luster A.D. (2006). CXCR3 requires tyrosine sulfation for ligand binding and a second extracellular loop arginine residue for ligand-induced chemotaxis. Mol Cell Biol 26, 5838-5849. (Pubitemid 44134338)
14. Etienne-Manneville S., Hall A. (2002). Rho GTPases in cell biology. Nature 420, 629-635. (Pubitemid 36764489)
15. Ferguson GJ et al. (2007). PI(3)Kgamma has an important context-dependent role in neutrophil chemokinesis. Nat Cell Biol 9, 86-91. (Pubitemid 46024201)
16. Filipenko NR, Attwell S, Roskelley C., Dedhar S. (2005). Integrin-linked kinase activity regulates Rac- and Cdc42-mediated actin cytoskeleton reorganization via alpha-PIX. Oncogene 24, 5837-5849. (Pubitemid 43080075)
17. Franca-Koh J., Kamimura Y, Devreotes P.N. (2007). Leading-edge research: PtdIns(3,4,5)P3 and directed migration. Nat Cell Biol 9, 15-17. (Pubitemid 46024189)
18. Frias MA, Thoreen CC, Jaffe J.D., Schroder W., Sculley T, Carr SA, Sabatini D.M. (2006). mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s. Curr Biol 16, 1865-1870. (Pubitemid 44354144)
19. Funamoto S, Milan K, Meili R., Firtel R.A. (2001). Role of phosphatidylinositol 3' kinase and a downstream pleckstrin homology domain-containing protein in controlling chemotaxis in Dictyostelium. J Cell Biol 153, 795-810.
20. Gao D et al. (2010). Rictor forms a complex with Cullin-1 to promote SGK1 ubiquitination and destruction. Mol Cell 39, 797-808.
21. Gomez-Mouton C., Lacalle RA, Mira E, Jimenez-Baranda S, Barber D.F., Carrera AC, Martinez AC, Manes S. (2004). Dynamic redistribution of raft domains as an organizing platform for signaling during cell chemotaxis. J Cell Biol 164, 759-768. (Pubitemid 38282959)
22. Hauert AB, Martinelli S, Marone C., Niggli V. (2002). Differentiated HL-60 cells are a valid model system for the analysis of human neutrophil migration and chemotaxis. Int J Biochem Cell Biol 34, 838-854. (Pubitemid 34304172)
23. He Y, Kapoor A, Cook S., Liu S, Xiang Y, Rao C.V., Kenis PJ, Wang F. (2011). The non-receptor tyrosine kinase Lyn controls neutrophil adhesion by recruiting the CrkL-C3G complex and activating Rap1 at the leading edge. J Cell Sci 124, 2153-2164.
24. Heit B, Liu L, Colarusso P., Puri KD, Kubes P. (2008). PI3K accelerates, but is not required for, neutrophil chemotaxis to fMLP. J Cell Sci 121, 205-214. (Pubitemid 351228453)
25. Hernandez-Negrete I., Carretero-Ortega J, Rosenfeldt H., Hernandez-Garcia R, Calderon-Salinas JV, Reyes-Cruz G, Gutkind J.S., Vazquez-Prado J (2007). P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration. J Biol Chem 282, 23708-23715. (Pubitemid 47311970)
26. Herzmark P, Campbell K, Wang F., Wong K, El-Samad H, Groisman A, Bourne H.R. (2007). Bound attractant at the leading vs. the trailing edge determines chemotactic prowess. Proc Natl Acad Sci USA 104, 13349-13354. (Pubitemid 47293948)
27. Hirsch E, Katanaev VL, Garlanda C, Azzolino O., Pirola L, Silengo L, Sozzani S., Mantovani A, Altruda F, Wymann M.P. (2000). Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science 287, 1049-1053.
28. Hoeller O, Kay R.R. (2007). Chemotaxis in the absence of PIP3 gradients. Curr Biol 17, 813-817. (Pubitemid 46635122)
29. Iden S, Collard J.G. (2008). Crosstalk between small GTPases and polarity proteins in cell polarization. Nat Rev Mol Cell Biol 9, 846-859.
30. Inoue T, Heo WD, Grimley J.S., Wandless TJ, Meyer T. (2005). An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways. Nat Methods 2, 415-418. (Pubitemid 40916559)
31. Inoue T, Meyer T. (2008). Synthetic activation of endogenous PI3K and Rac identifies an AND-gate switch for cell polarization and migration. PLoS ONE 3, e3068.
32. Jacinto E, Facchinetti V, Liu D., Soto N, Wei S, Jung S Y, Huang Q, Qin J., Su B. (2006). SIN1/MIP1 maintains Rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell 127, 125-137. (Pubitemid 44466632)
33. Jacinto E, Loewith R, Schmidt A., Lin S, Ruegg MA, Hall A, Hall M.N. (2004). Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 6, 1122-1128. (Pubitemid 39468014)
34. Kamada Y, Fujioka Y, Suzuki N.N., Inagaki F., Wullschleger S, Loewith R, Hall M.N., Ohsumi Y. (2005). Tor2 directly phosphorylates the AGC kinase Ypk2 to regulate actin polarization. Mol Cell Biol 25, 7239-7248. (Pubitemid 41105919)
35. Kamimura Y, Xiong Y, Iglesias P.A., Hoeller O., Bolourani P, Devreotes P.N. (2008). PIP3-independent activation of TorC2 and PKB at the cell's leading edge mediates chemotaxis. Curr Biol 18, 1034-1043.
36. Knall C, Worthen GS, Johnson G.L. (1997). Interleukin 8-stimulated phosphatidylinositol-3-kinase activity regulates the migration of human neutrophils independent of extracellular signal-regulated kinase and p38 mitogen-activated protein kinases. Proc Natl Acad Sci USA 94, 3052-3057.
37. Kunisaki Y et al. (2006). DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. J Cell Biol 174, 647-652.
38. Lee S, Comer FI, Sasaki A, McLeod I.X., Duong Y., Okumura K, Yates JR 3rd, Parent CA, Firtel RA (2005). TOR complex 2 integrates cell movement during chemotaxis and signal relay in Dictyostelium. Mol Biol Cell 16, 4572-4583. (Pubitemid 41416442)
39. Li Z et al. (2003). Directional sensing requires G beta gamma-mediated PAK1 and PIX alpha-dependent activation of Cdc42. Cell 114, 215-227. (Pubitemid 36936915)
40. Li Z, Jiang H, Xie W., Zhang Z, Smrcka AV, Wu D. (2000). Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant-mediated signal transduction. Science 287, 1046-1049. (Pubitemid 30094361)
41. Liu L, Das S, Losert W., Parent C.A. (2010). mTORC2 regulates neutrophil chemotaxis in a cAMP- and RhoA-dependent fashion. Dev Cell 19, 845-857.
42. Loewith R, Jacinto E, Wullschleger S., Lorberg A, Crespo JL, Bonenfant D, Oppliger W., Jenoe P, Hall M.N. (2002). Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 10, 457-468. (Pubitemid 35284167)
43. McDonald PC, Oloumi A, Mills J., Dobreva I, Maidan M, Gray V., Wederell ED, Bally MB, Foster LJ, Dedhar S. (2008). Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and cancer cell survival. Cancer Res 68, 1618-1624. (Pubitemid 351416544)
44. Meili R, Ellsworth C, Lee S., Reddy TB, Ma H, Firtel R.A. (1999). Chemoattractant-mediated transient activation and membrane localization of Akt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium. EMBO J 18, 2092-2105. (Pubitemid 29179167)
45. Neel NF, Barzik M, Raman D., Sobolik-Delmaire T, Sai J, Ham A.J., Mernaugh RL, Gertler FB, Richmond A. (2009). VASP is a CXCR2-interacting protein that regulates CXCR2-mediated polarization and chemotaxis. J Cell Sci 122, 1882-1894.
46. Nishio M et al. (2007). Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1. Nat Cell Biol 9, 36-44. (Pubitemid 46024195)
47. Nuzzi PA, Senetar MA, Huttenlocher A. (2007). Asymmetric localization of calpain 2 during neutrophil chemotaxis. Mol Biol Cell 18, 795-805. (Pubitemid 46399486)
48. Parent CA, Blacklock BJ, Froehlich W.M., Murphy DB, Devreotes P.N. (1998). G protein signaling events are activated at the leading edge of chemotactic cells. Cell 95, 81-91. (Pubitemid 28458026)
49. Pestonjamasp KN, Forster C, Sun C., Gardiner EM, Bohl B, Weiner O, Bokoch G.M., Glogauer M. (2006). Rac1 links leading edge and uropod events through Rho and myosin activation during chemotaxis. Blood 108, 2814-2820.
50. Price LS, Leng J, Schwartz M.A., Bokoch G.M. (1998). Activation of Rac and Cdc42 by integrins mediates cell spreading. Mol Biol Cell 9, 1863-1871. (Pubitemid 28337528)
51. Rickert P, Weiner OD, Wang F, Bourne H.R., Servant G. (2000). Leukocytes navigate by compass: roles of PI3Kgamma and its lipid products. Trends Cell Biol 10, 466-473.
52. Roberts AW et al. (1999). Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. Immunity 10, 183-196. (Pubitemid 29115624)
53. Saci A, Cantley LC, Carpenter C.L. (2011). Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size. Mol Cell 42, 50-61.
54. Sanchez-Madrid F., del Pozo MA (1999). Leukocyte polarization in cell migration and immune interactions. EMBO J 18, 501-511. (Pubitemid 29057235)
55. Sander EE, ten Klooster J P, van Delft S, van der Kammen RA, Collard JG (1999). Rac downregulates Rho activity: reciprocal balance between both GTPases determines cellular morphology and migratory behavior. J Cell Biol 147, 1009-1022.
56. Sarbassov DD, Ali SM, Kim D.H., Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini D.M. (2004). Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 14, 1296-1302. (Pubitemid 38991819)
57. Sarbassov DD, Ali SM, Sabatini D.M. (2005a). Growing roles for the mTOR pathway. Curr Opin Cell Biol 17, 596-603. (Pubitemid 41540408)
58. Sarbassov DD, Guertin DA, Ali S.M., Sabatini D.M. (2005b). Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307, 1098-1101. (Pubitemid 40262113)
59. Sasaki T et al. (2000). Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration. Science 287, 1040-1046.
60. Schmidt A, Kunz J, Hall M.N. (1996). TOR2 is required for organization of the actin cytoskeleton in yeast. Proc Natl Acad Sci USA 93, 13780-13785. (Pubitemid 26424197)
61. Schymeinsky J, Sindrilaru A, Frommhold D., Sperandio M, Gerstl R, Then C., Mocsai A, Scharffetter-Kochanek K, Walzog B. (2006). The Vav binding site of the non-receptor tyrosine kinase Syk at Ty r 348 is critical for β2 integrin (CD11/CD18)-mediated neutrophil migration. Blood 108, 3919-3927. (Pubitemid 44864578)
62. Servant G, Weiner OD, Herzmark P, Balla T., Sedat JW, Bourne H.R. (2000). Polarization of chemoattractant receptor signaling during neutrophil chemotaxis. Science 287, 1037-1040. (Pubitemid 30094359)
63. Shin ME et al. (2010). Spatiotemporal organization, regulation, and functions of tractions during neutrophil chemotaxis. Blood 116, 3297-3310.
64. Srinivasan S, Wang F, Glavas S., Ott A, Hofmann F, Aktories K., Kalman D, Bourne H.R. (2003). Rac and Cdc42 play distinct roles in regulating PI(3,4,5) P3 and polarity during neutrophil chemotaxis. J Cell Biol 160, 375-385. (Pubitemid 36182728)
65. Thoreen CC, Kang SA, Chang J.W., Liu Q., Zhang J, Gao Y, Reichling L.J., Sim T., Sabatini DM, Gray N.S. (2009). An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem 284, 8023-8032.
66. Van Keymeulen A., Wong K, Knight Z.A., Govaerts C., Hahn KM, Shokat KM, Bourne H.R. (2006). To stabilize neutrophil polarity, PIP3 and Cdc42 augment RhoA activity at the back as well as signals at the front. J Cell Biol 174, 437-445. (Pubitemid 44156773)
67. Vilella-Bach M., Nuzzi P, Fang Y., Chen J. (1999). The FKBP12-rapamycin-binding domain is required for FKBP12-rapamycin-associated protein kinase activity and G1 progression. J Biol Chem 274, 4266-4272.
68. Wang F (2009). The signaling mechanisms underlying cell polarity and chemotaxis. Cold Spring Harb Perspect Biol 1, a002980.
69. Wang F, Herzmark P, Weiner O.D., Srinivasan S., Servant G, Bourne H.R. (2002). Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils. Nat Cell Biol 4, 513-518. (Pubitemid 34752437)
70. Weiner OD (2002). Regulation of cell polarity during eukaryotic chemotaxis: the chemotactic compass. Curr Opin Cell Biol 14, 196-202. (Pubitemid 34219509)
71. Weiner OD, Rentel MC, Ott A, Brown G.E., Jedrychowski M., Yaffe MB, Gygi S P, Cantley LC, Bourne H.R., Kirschner M.W. (2006). Hem-1 complexes are essential for Rac activation, actin polymerization, and myosin regulation during neutrophil chemotaxis. PLoS Biol 4, e38.
72. Williams DA et al. (2000). Dominant negative mutation of the hematopoietic-specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency. Blood 96, 1646-1654. (Pubitemid 30661042)
73. Wullschleger S, Loewith R, Hall M.N. (2006). TOR signaling in growth and metabolism. Cell 124, 471-484. (Pubitemid 43199434)
74. Xu J, Wang F, Van Keymeulen A, Herzmark P, Straight A., Kelly K, Takuwa Y, Sugimoto N., Mitchison T, Bourne HR (2003). Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell 114, 201-214. (Pubitemid 36936914)
75. Xu J, Wang F, Van Keymeulen A, Rentel M, Bourne H.R. (2005). Neutrophil microtubules suppress polarity and enhance directional migration. Proc Natl Acad Sci USA 102, 6884-6889. (Pubitemid 40675411)
76. Yang Q, Inoki K, Ikenoue T., Guan K.L. (2006). Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity. Genes Dev 20, 2820-2832. (Pubitemid 44771744)
77. Zhou J et al. (2009). mTOR supports long-term self-renewal and suppresses mesoderm and endoderm activities of human embryonic stem cells. Proc Natl Acad Sci USA 106, 7840-7845.