Dynamics of the rho-family small GTPases in actin regulation and motility

Cell Adhesion and Migration

Volumn 5, Issue 2, 2011, Pages 170-180

  Spiering, Désirée ^a   Hodgson, Louis ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

Actin; Biosensors; Dynamics; FRET; Live cell imaging; Migration; Rho

Indexed keywords

ACTIN; GUANOSINE TRIPHOSPHATASE; RHO FACTOR;

CELL MIGRATION; CELL MOTILITY; CYTOSKELETON; FLUORESCENCE RESONANCE ENERGY TRANSFER; GENE TARGETING; IN VIVO CULTURE; NONHUMAN; PROTEIN LOCALIZATION; REVIEW;

EID: 79952352658     PISSN: 19336918     EISSN: 19336926     Source Type: Journal    
DOI: 10.4161/cam.5.2.14403     Document Type: Review

References (135)

1. Bourne HR, Sanders DA, McCormick F. The GTPase superfamily: conserved structure and molecular mechanism. Nature 1991; 349:117-27. (Pubitemid 21912023)
2. Hall A. Ras-related GTPases and the cytoskeleton. Mol Biol Cell 1992; 3:475-9.
3. Nobes CD, Hall A. Regulation and function of the Rho subfamily of small GTPases. Cur Opin Genet Dev 1994; 4:77-81. (Pubitemid 24060299)
4. Nobes CD, Hall A. Rho, Rac and Cdc42 GTPases: regulators of actin structures, cell adhesion and motility. Biochem Soc Transactions 1995; 23:456-9.
5. Nobes CD, Hall A. Rho, rac and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia and filopodia. Cell 1995; 81:53-62.
6. Ridley AJ, Hall A. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 1992; 70:389-99.
7. Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 1992; 70:401-10.
8. Norman JC, Price LS, Ridley AJ, Hall A, Koffer A. Actin filament organization in activated mast cells in regulated by heterotrimeric and small GTP-binding proteins. J Cell Biol 1994; 126:1005-15. (Pubitemid 24252146)
9. Ridley AJ, Hall A. Signal transduction pathways regulating Rho-mediated stress fiber formation: requirement for a tyrosine kinase. EMBO J 1994; 13:2600-10. (Pubitemid 24188393)
10. Chrzanowska-Wodnicka M, Burridge K. Rhos-timulated contractility drives the formation of stress fibers and focal adhesions. J Cell Biol 1996; 133:1403-15. (Pubitemid 26192339)
11. Machesky LM, Hall A. Role of actin polymerization and adhesion to extracellular matrix in Rac- and Rho-induced cytoskeletal reorganization. J Cell Biol 1997; 138:913-26. (Pubitemid 27365052)
12. Subauste MC, Von Herrath M, Benard V, Chamberlain CE, Chuang TH, Chu K, et al. Rho family proteins modulate rapid apoptosis induced by cytotoxic T lymphocytes and Fas. J Biol Chem 2000; 275:9725-33. (Pubitemid 30185206)
13. Bourne HR, Sanders DA, McCormick F. The GTPase superfamily: a conserved switch for diverse cell functions. Nature 1990; 348:125.
14. Gibbs JB, Marshall MS, Scohick EM, Dixon RAF, Vogel US. Modulation of guanine nucleotide bound to Rac in NIH3T3 cells by oncogenes, growth factors and the GTPase activating protein (GAP). J Biol Chem 1990; 265:20437-42. (Pubitemid 120014028)
15. Rossman KL, Der CJ, Sondek J. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol 2005; 6:167-80. (Pubitemid 40215811)
16. Snyder JT, Worthylake DK, Rossman KL, Betts L, Pruitt WM, Siderovski DP, et al. Structural basis for the selective activation of Rho GTPases by Dbl exchange factors. Nat Struct Biol 2002; 9:468-75. (Pubitemid 34568794)
17. Fujisawa K, Fujita A, Ishizaki T, Saito Y, Narumiya S. Identification of the Rho-binding domain of p160ROCK, a Rho-associated coiled-coil containing protein kinase. J Biol Chem 1996; 271:23022-8. (Pubitemid 26314733)
18. Reid T, Furuyashiki T, Ishizaki T, Watanabe G, Watanabe N, Fujisawa K, et al. Rhotekin, a new putative target for Rho bearing homology to a serine/threonine kinase, PKN and rhophilin in the rho-binding domain. J Biol Chem 1996; 271:13556-60. (Pubitemid 26185401)
19. Fujisawa K, Madaule P, Ishizaki T, Watanabe G, Bito H, Saito Y, et al. Different regions of Rho determine Rho-selective binding of different classes of Rho target molecules. J Biol Chem 1998; 273:18943-9. (Pubitemid 28366283)
20. Rossman KL, Worthylake DK, Snyder JT, Siderovski DP, Campbell SL, Sondek J. A crystallographic view of interactions between Dbs and Cdc42: PH domain-assisted guanine nucleotide exchange. EMBO J 2002; 21:1315-26. (Pubitemid 34246510)
21. Fidyk NJ, Cerione RA. Understanding the catalytic mechanism of GTPase-activating proteins: demonstration of the importance of switch domain stabilization in the stimulation of GTP hydrolysis. Biochemistry 2002; 41:15644-53. (Pubitemid 36062469)
22. Moon SY, Zheng Y. Rho GTPase-activating proteins in cell regulation. Trends Cell Biol 2003; 13:13-22. (Pubitemid 35453891)
23. Zhang B, Zheng Y. Regulation of RhoA GTP hydrolysis by the GTPase-activating proteins p190, p50RhoGAP, Bcr and 3BP-1. Biochemistry 1998; 37:5249-57. (Pubitemid 28176526)
24. Hart MJ, Maru Y, Leonard D, Witte ON, Evans T, Cerione RA. A GDP dissociation inhibitor that serves as a GTPase inhibitor for the Ras-like protein CDC42Hs. Science 1992; 258:812-5.
25. Chuang TH, Bohl BP, Bokoch GM. Biologically active lipids are regulators of Rac:GDI complexation. J Biol Chem 1993; 268:26206-11. (Pubitemid 23361688)
26. Chuang TH, Xu X, Knaus UG, Hart MJ, Bokoch GM. GDP dissociation inhibitor (GDI) prevents intrinsic and GTPase activating protein (GAP)-stimulated GTP hydrolysis by the Rac1 and Rac2 GTP-binding proteins. J Biol Chem 1993; 268:775-8. (Pubitemid 23019701)
27. Bokoch GM, Bohl BP, Chuang TH. Guanine nucleotide exchange regulates membrane translocation of Rac/Rho GTP-binding proteins. J Biol Chem 1994; 269:31674-9. (Pubitemid 24379533)
28. DerMardirossian C, Bokoch GM. GDIs: central regulatory molecules in Rho GTPase activation. Trends Cell Biol 2005; 15:356-63. (Pubitemid 40943524)
29. DerMardirossian C, Rocklin G, Seo JY, Bokoch GM. Phosphorylation of RhoGDI by Src regulates Rho GTPase binding and cytosol-membrane cycling. Mol Biol Cell 2006; 17:4760-8. (Pubitemid 44665745)
30. Qiao J, Holian O, Lee BS, Huang F, Zhang J, Lum H. Phosphorylation of GTP dissociation inhibitor by PKA negatively regulates RhoA. Am J Physiol Cell Physiol 2008; 295:1161-8.
31. Dovas A, Choi Y, Yoneda A, Multhaupt HA, Kwon SH, Kang D, et al. Serine 34 phosphorylation of rho guanine dissociation inhibitor (RhoGDIalpha) links signaling from conventional protein kinase C to RhoGTPase in cell adhesion. J Biol Chem 2010; 285:23296-308.
32. Sasaki T, Kato M, Takai Y. Consequences of weak interaction of rho GDI with the GTP-bound forms of rho p21 and rac p21. J Biol Chem 1993; 268:23959-63. (Pubitemid 23335372)
33. Berdeaux RL, Diaz B, Kim L, Martin GS. Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function. J Cell Biol 2004; 166:317-23. (Pubitemid 39031235)
34. Buccione R, Orth JD, McNiven MA. Foot and mouth: podosomes, invadopodia and circular dorsal ruffles. Nat Rev Mol Cell Biol 2004; 5:647-57. (Pubitemid 39025065)
35. Yamaguchi H, Lorenz M, Kempiak S, Sarmiento C, Coniglio S, Symons M, et al. Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/ 3 complex pathway and cofilin. J Cell Biol 2005; 168:441-52. (Pubitemid 40205066)
36. Sander EE, ten Klooster JP, van Delft S, van der Kammen RA, Collard JG. Rac downregulates Rho activity: reciprocal balance between both GTPases determines cellular morphology and migratory behavior. J Cell Biol 1999; 147:1009-22.
37. Machacek M, Hodgson L, Welch C, Elliott H, Pertz O, Nalbant P, et al. Coordination of Rho GTPase activities during cell protrusion. Nature 2009; 461:99-103.
38. Hoppe AD, Swanson JA. Cdc42, Rac1 and Rac2 display distinct patterns of activation during phagocytosis. Mol Biol Cell 2004; 15:3509-19.
39. Kozma R, Sarner S, Ahmed S, Lim L. Rho family GTPases and neuronal growth cone remodelling: relationship between increased complexity induced by Cdc42Hs, Rac1 and acetylcholine and collapse induced by RhoA and lysophosphatidic acid. Mol Cell Biol 1997; 17:1201-11.
40. Leeuwen FN, Kain HE, Kammen RA, Michiels F, Kranenburg OW, Collard JG. The guanine nucleotide exchange factor Tiam1 affects neuronal morphology; opposing roles for the small GTPases Rac and Rho. J Cell Biol 1997; 139:797-807. (Pubitemid 27485843)
41. Wang F, Herzmark P, Weiner OD, Srinivasan S, Servant G, Bourne HR. Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils. Nat Cell Biol 2002; 4:513-8.
42. Van Keymeulen A, Wong K, Knight ZA, Govaerts C, Hahn KM, Shokat KM, et al. To stabilize neutrophil polarity, PIP3 and Cdc42 augment RhoA activity at the back as well as signals at the front. J Cell Biol 2006; 174:437-45. (Pubitemid 44156773)
43. Wong K, Pertz O, Hahn K, Bourne H. Neutrophil polarization: spatiotemporal dynamics of RhoA activity support a self-organizing mechanism. Proc Natl Acad Sci USA 2006; 103:3639-44. (Pubitemid 43376608)
44. Rottner K, Hall A, Small JV. Interplay between Rac and Rho in the control of substrate contact dynamics. Curr Biol 1999; 9:640-8. (Pubitemid 29291944)
45. Yamana N, Arakawa Y, Nishino T, Kurokawa K, Tanji M, Itoh RE, et al. The Rho-mDia1 pathway regulates cell polarity and focal adhesion turnover in migrating cells through mobilizing Apc and c-Src. Mol Cell Biol 2006; 26:6844-58. (Pubitemid 44387634)
46. Kraynov VS, Chamberlain C, Bokoch GM, Schwartz MA, Slabaugh S, Hahn KM. Localized Rac activation dynamics visualized in living cells. Science 2000; 290:333-7.
47. Nalbant P, Hodgson L, Kraynov V, Toutchkine A, Hahn KM. Activation of endogenous Cdc42 visualized in living cells. Science 2004; 305:1615-9. (Pubitemid 39296355)
48. Pertz O, Hodgson L, Klemke RL, Hahn KM. Spatiotemporal dynamics of RhoA activity in migrating cells. Nature 2006; 440:1069-72.
49. Shen F, Hodgson L, Rabinovich A, Pertz O, Hahn K, Price JH. Functional proteometrics for cell migration. Cytometry A 2006.
50. Healy KD, Hodgson L, Kim TY, Shutes A, Maddileti S, Juliano RL, et al. DLC-1 suppresses non-small cell lung cancer growth and invasion by RhoGAP-dependent and independent mechanisms. Mol Carcinog 2007; 47: 326-37.
51. Narumiya S, Tanji M, Ishizaki T. Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion. Cancer Metastasis Rev 2009; 28:65-76.
52. Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, et al. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science 1999; 285:895-8. (Pubitemid 29381991)
53. Riento K, Ridley AJ. Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol 2003; 4:446-56. (Pubitemid 36648590)
54. Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K. Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J Biol Chem 2000; 275:3577-82. (Pubitemid 30083067)
55. Lin T, Zeng L, Liu Y, DeFea K, Schwartz MA, Chien S, et al. Rho-ROCK-LIMK-cofilin pathway regulates shear stress activation of sterol regulatory element binding proteins. Circ Res 2003; 92:1296-304. (Pubitemid 36773471)
56. Song X, Chen X, Yamaguchi H, Mouneimne G, Condeelis JS, Eddy RJ. Initiation of cofilin activity in response to EGF is uncoupled from cofilin phosphorylation and dephosphorylation in carcinoma cells. J Cell Sci 2006; 119:2871-81. (Pubitemid 44177865)
57. Bernstein BW, Painter WB, Chen H, Minamide LS, Abe H, Bamburg JR. Intracellular pH modulation of ADF/cofilin proteins. Cell Motil Cytoskeleton 2000; 47:319-36.
58. Bowman GD, Nodelman IM, Hong Y, Chua NH, Lindberg U, Schutt CE. A comparative structural analysis of the ADF/cofilin family. Proteins 2000; 41:374-84.
59. DesMarais V, Ichetovkin I, Condeelis J, Hitchcock-DeGregori SE. Spatial regulation of actin dynamics: a tropomyosin-free, actin-rich compartment at the leading edge. J Cell Sci 2002; 115:4649-60. (Pubitemid 36007758)
60. Zigmond SH. Beginning and ending an actin filament: control at the barbed end. Curr Top Dev Biol 2004; 63:145-88. (Pubitemid 39752387)
61. Andrianantoandro E, Pollard TD. Mechanism of actin filament turnover by severing and nucleation at different concentrations of ADF/cofilin. Mol Cell 2006; 24:13-23. (Pubitemid 44466682)
62. Bamburg JR, Bernstein BW. ADF/cofilin. Curr Biol 2008; 18:273-5.
63. Bernstein BW, Bamburg JR. ADF/cofilin: a functional node in cell biology. Trends Cell Biol 2010; 20:187-95.
64. DesMarais V, Ghosh M, Eddy R, Condeelis J. Cofilin takes the lead. J Cell Sci 2005; 118:19-26. (Pubitemid 40277101)
65. van Rheenen J, Condeelis J, Glogauer M. A common cofilin activity cycle in invasive tumor cells and inflammatory cells. J Cell Sci 2009; 122:305-11.
66. Oser M, Condeelis J. The cofilin activity cycle in lamellipodia and invadopodia. J Cell Biochem 2009; 108:1252-62.
67. Condeelis J. How is actin polymerization nucleated in vivo? Trends Cell Biol 2001; 11:288-93.
68. Edwards DC, Sanders LC, Bokoch GM, Gill GN. Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics [see comments]. Nat Cell Biol 1999; 1:253-9. (Pubitemid 129495774)
69. Kligys K, Claiborne JN, DeBiase PJ, Hopkinson SB, Wu Y, Mizuno K, et al. The slingshot family of phosphatases mediates Rac1 regulation of cofilin phosphorylation, laminin-332 organization and motility behavior of keratinocytes. J Biol Chem 2007; 282:32520-8. (Pubitemid 350106481)
70. Huang TY, DerMardirossian C, Bokoch GM. Cofilin phosphatases and regulation of actin dynamics. Curr Opin Cell Biol 2006; 18:26-31. (Pubitemid 43107604)
71. Goode BL, Eck MJ. Mechanism and function of formins in the control of actin assembly. Annu Rev Biochem 2007; 76:593-627.
72. Shemesh T, Kozlov MM. Actin polymerization upon processive capping by formin: a model for slowing and acceleration. Biophys J 2007; 92:1512-21. (Pubitemid 46393463)
73. Romero S, Le Clainche C, Didry D, Egile C, Pantaloni D, Carlier MF. Formin is a processive motor that requires profilin to accelerate actin assembly and associated ATP hydrolysis. Cell 2004; 119:419-29. (Pubitemid 39423843)
74. Zigmond SH. Formin-induced nucleation of actin filaments. Curr Opin Cell Biol 2004; 16:99-105. (Pubitemid 38368159)
75. Zigmond SH, Evangelista M, Boone C, Yang C, Dar AC, Sicheri F, et al. Formin leaky cap allows elongation in the presence of tight capping proteins. Curr Biol 2003; 13:1820-3. (Pubitemid 37269124)
76. Lammers M, Meyer S, Kuhlmann D, Wittinghofer A. Specificity of interactions between mDia isoforms and Rho proteins. J Biol Chem 2008; 283:35236-46.
77. Bartolini F, Moseley JB, Schmoranzer J, Cassimeris L, Goode BL, Gundersen GG. The formin mDia2 stabilizes microtubules independently of its actin nucleation activity. J Cell Biol 2008; 181:523-36. (Pubitemid 351645041)
78. Palazzo AF, Cook TA, Alberts AS, Gundersen GG. mDia mediates Rho-regulated formation and orientation of stable microtubules. Nat Cell Biol 2001; 3:723-9. (Pubitemid 32734250)
79. Wen Y, Eng CH, Schmoranzer J, Cabrera-Poch N, Morris EJ, Chen M, et al. EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. Nat Cell Biol 2004; 6:820-30. (Pubitemid 39207247)
80. Symons M, Derry JM, Karlak B, Jiang S, Lemahieu V, McCormick F, et al. Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization. Cell 1996; 84:723-34. (Pubitemid 26094202)
81. Kempiak SJ, Yamaguchi H, Sarmiento C, Sidani M, Ghosh M, Eddy RJ, et al. A neural Wiskott-Aldrich Syndrome protein-mediated pathway for localized activation of actin polymerization that is regulated by cortactin. J Biol Chem 2005; 280:5836-42. (Pubitemid 40280065)
82. Derivery E, Gautreau A. Generation of branched actin networks: assembly and regulation of the N-WASP and WAVE molecular machines. BioEssays 2010; 32:119-31.
83. Takenawa T, Miki H. WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell movement. J Cell Sci 2001; 114:1801-9. (Pubitemid 32530035)
84. Nakagawa H, Miki H, Ito M, Ohashi K, Takenawa T, Miyamoto S. N-WASP, WAVE and Mena play different roles in the organization of actin cytoskeleton in lamellipodia. J Cell Sci 2001; 114:1555-65. (Pubitemid 32427841)
85. Miki H, Suetsugu S, Takenawa T. WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac. EMBO J 1998; 17:6932-41. (Pubitemid 28550287)
86. Takenawa T. From N-WASP to WAVE: key molecules for regulation of cortical actin organization. Novartis Found Symp 2005; 269:3-10.
87. Nakanishi O, Suetsugu S, Yamazaki D, Takenawa T. Effect of WAVE2 phosphorylation on activation of the Arp2/3 complex. J Biochem 2007; 141:319-25. (Pubitemid 46770384)
88. Ishiguro K, Cao Z, Ilasca ML, Ando T, Xavier R. Wave2 activates serum response element via its VCA region and functions downstream of Rac. Exp Cell Res 2004; 301:331-7. (Pubitemid 39504984)
89. Miki H, Takenawa T. Regulation of actin dynamics by WASP family proteins. J Biochem 2003; 134:309-13. (Pubitemid 37288327)
90. She HY, Rockow S, Tang J, Nishimura R, Skolnik EY, Chen M, et al. Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living cells. Mol Biol Cell 1997; 8:1709-21. (Pubitemid 27411136)
91. Carlier MF, Nioche P, Broutin-L'Hermite I, Boujemaa R, Le Clainche C, Egile C, et al. GRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott-Aldrich syndrome protein (N-WASp) with actin-related protein (ARP2/3) complex. J Biol Chem 2000; 275:21946-52. (Pubitemid 30621767)
92. Benesch S, Lommel S, Steffen A, Stradal TE, Scaplehorn N, Way M, et al. Phosphatidylinositol 4,5-biphosphate (PIP2)-induced vesicle movement depends on N-WASP and involves Nck WIP and Grb2. J Biol Chem 2002; 277:37771-6.
93. Miki H, Yamaguchi H, Suetsugu S, Takenawa T. IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling. Nature 2000; 408:732-5. (Pubitemid 32015990)
94. Ismail AM, Padrick SB, Chen B, Umetani J, Rosen MK. The WAVE regulatory complex is inhibited. Nat Struct Mol Biol 2009; 16:561-3.
95. Derivery E, Lombard B, Loew D, Gautreau A. The Wave complex is intrinsically inactive. Cell Motil Cytoskeleton 2009; 66:777-90.
96. Lundquist EA. Small GTPases. WormBook 2006; 1-18.
97. Johnson DI. Cdc42: An essential Rho-type GTPase controlling eukaryotic cell polarity. Microbiol Mol Biol Rev 1999; 63:54-105. (Pubitemid 29116087)
98. Bielek H, Anselmo A, Dermardirossian C. Morphological and proliferative abnormalities in renal mesangial cells lacking RhoGDI. Cell Signal 2009; 21:1974-83.
99. Del Pozo MA, Kiosses WB, Alderson NB, Meller N, Hahn KM, Schwartz MA. Integrins regulate GTP-Rac localized effector interactions through dissociation of Rho-GDI. Nat Cell Biol 2002; 4:232-9.
100. Michaelson D, Silletti J, Murphy G, D'Eustachio P, Rush M, Philips MR. Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding. J Cell Biol 2001; 152:111-26.
101. Ren XD, Schwartz MA. Determination of GTP loading on Rho. Methods Enzymol 2000; 325:264-72.
102. Benard V, Bokoch GM. Assay of Cdc42, Rac and Rho GTPase activation by affinity methods. Methods Enzymol 2002; 345:349-59.
103. Cho SY, Klemke RL. Purification of pseudopodia from polarized cells reveals redistribution and activation of Rac through assembly of a CAS/Crk scaffold. J Cell Biol 2002; 156:725-36.
104. Taylor DL, Wang YL. Fluorescently labeled molecules as probes of the structure and function of living cells. Nature 1980; 284:405-10.
105. Tsien RY, Miyawaki A. Seeing the machinery of live cells. Science 1998; 280:1954-5.
106. 2+ measurements using improved cameleons. Proc Natl Acad Sci USA 1999; 96:2135-40.
107. Zaccolo M, De Giorgi F, Cho CY, Feng L, Knapp T, Negulescu PA, et al. A genetically encoded, fluorescent indicator for cyclic AMP in living cells. Nat Cell Biol 2000; 2:25-9.
108. Chalfie M, Tu Y, Euskirchen G, Ward WW, Prasher DC. Green fluorescent protein as a marker for gene expression. Science 1994; 263:802-5.
109. Heim R, Tsien RY. Engineering green fluorescent protein for improved brightness, longer wavelengths and fluorescence resonance energy transfer. Curr Biol 1996; 6:178-82.
110. Adams SR, Harootunian AT, Buechler YJ, Taylor SS, Tsien RY. Fluorescence ratio imaging of cyclic AMP in single cells. Nature 1991; 349:694-7.
111. Hahn K, DeBiasio R, Taylor DL. Patterns of elevated free calcium and calmodulin activation in living cells. Nature 1992; 359:736-8.
112. 2+ based on green fluorescent proteins and calmodulin [see comments]. Nature 1997; 388:882-7.
113. Llopis J, Westin S, Ricote M, Wang Z, Cho CY, Kurokawa R, et al. Ligand-dependent interactions of coactivators steroid receptor coactivator-1 and peroxisome proliferator-activated receptor binding protein with nuclear hormone receptors can be imaged in live cells and are required for transcription. Proc Natl Acad Sci USA 2000; 97:4363-8.
114. Ting AY, Kain KH, Klemke RL, Tsien RY. Genetically encoded fluorescent reporters of protein tyrosine kinase activities in living cells. Proc Natl Acad Sci USA 2001; 98:15003-8.
115. Haj FG, Verveer PJ, Squire A, Neel BG, Bastiaens PI. Imaging sites of receptor dephosphorylation by PTP1B on the surface of the endoplasmic reticulum. Science 2002; 295:1708-11.
116. Heikal AA, Hess ST, Baird GS, Tsien RY, Webb WW. Molecular spectroscopy and dynamics of intrinsically fluorescent proteins: coral red (dsRed) and yellow (Citrine). Proc Natl Acad Sci USA 2000; 97:11996-2001.
117. Miyawaki A, Tsien RY. Monitoring protein conformations and interactions by fluorescence resonance energy transfer between mutants of green fluorescent protein. Methods Enzymol 2000; 327:472-500.
118. Nguyen AW, Daugherty PS. Evolutionary optimization of fluorescent proteins for intracellular FRET. Nat Biotechnol 2005; 23:355-60.
119. Griesbeck O, Baird GS, Campbell RE, Zacharias DA, Tsien RY. Reducing the environmental sensitivity of yellow fluorescent protein. Mechanism and applications. J Biol Chem 2001; 276:29188-94.
120. Lakowicz JR. Principles of Fluorescence Spectroscopy. New York: Kluwer Academic/Plenum Publishers 1999; 368-77.
121. dos Remedios CG, Moens PD. Fluorescence resonance energy transfer spectroscopy is a reliable "ruler" for measuring structural changes in proteins. Dispelling the problem of the unknown orientation factor. J Struct Biol 1995; 115:175-85.
122. Nagai T, Yamada S, Tominaga T, Ichikawa M, Miyawaki A. Expanded dynamic range of fluorescent indicators for Ca(2+) by circularly permuted yellow fluorescent proteins. Proc Natl Acad Sci USA 2004; 101:10554-9.
123. Machacek M, Hodgson L, Welch C, Elliot H, Nalbant P, Pertz O, et al. Coordination of Rho GTPase activation during protrusion. Nature 2009; 461:99-103.
124. Ouyang M, Huang H, Shaner NC, Remacle AG, Shiryaev SA, Strongin AY, et al. Simultaneous visualization of protumorigenic Src and MT1-MMP activities with fluorescence resonance energy transfer. Cancer Res 2010; 70:2204-12.
125. Ameloot M, Beechem JM, Brand L. Simultaneous analysis of multiple fluorescence decay curves by Laplace Transforms: Deconvolution with reference or excitation profiles. Biophys Chem 1986; 23:155-71.
126. Verveer PJ, Squire A, Bastiaens PI. Improved spatial discrimination of protein reaction states in cells by global analysis and deconvolution of fluorescence lifetime imaging microscopy data. J Microsc 2001; 202:451-6.
127. Le Puil M, Biggerstaff JP, Weidow BL, Price JR, Naser SA, White DC, et al. A novel fluorescence imaging technique combining deconvolution microscopy and spectral analysis for quantitative detection of opportunistic pathogens. J Microbiol Methods 2006; 67:597-602.
128. Pepperkok R, Squire A, Geley S, Bastiaens PI. Simultaneous detection of multiple green fluorescent proteins in live cells by fluorescence lifetime imaging microscopy. Curr Biol 1999; 9:269-72.
129. Machacek M, Danuser G. Morphodynamic profiling of protrusion phenotypes. Biophys J 2006; 90:1439-52.
130. Wu YI, Frey D, Lungu OI, Jaehrig A, Schlichting I, Kuhlman B, et al. A genetically encoded photoactivatable Rac controls the motility of living cells. Nature 2009; 461:104-8.
131. Levskaya A, Weiner OD, Lim WA, Voigt CA. Spatiotemporal control of cell signalling using a light-switchable protein interaction. Nature 2009; 461:997-1001.
132. Hodgson L, Nalbant P, Shen F, Hahn K. Imaging and photobleach correction of Mero-CBD, sensor of endogenous Cdc42 activation. Methods Enzymol 2006; 406:140-56.
133. Hodgson L, Pertz O, Hahn KM. Design and optimization of genetically encoded fluorescent biosensors: GTPase biosensors. Methods Cell Biol 2008; 85:63-81.
134. Hodgson L, Shen F, Hahn K. Biosensors for characterizing the dynamics of rho family GTPases in living cells. Curr Protoc Cell Biol 2010; 14:1-26.
135. Itoh RE, Kurokawa K, Ohba Y, Yoshizaki H, Mochizuki N, Matsuda M. Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells. Mol Cell Biol 2002; 22:6582-91.