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RHO GTPase Signaling for Axon Extension: Is Prenylation Important?

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Abstract

Many lines of evidence indicate the importance of the Rho family guanine nucleotide triphosphatases (GTPases) in directing axon extension and guidance. The signaling networks that involve these proteins regulate actin cytoskeletal dynamics in navigating neuronal growth cones. However, the intricate patterns that regulate Rho GTPase activation and signaling are not yet fully defined. Activity and subcellular localization of the Rho GTPases are regulated by post-translational modification. The addition of a geranylgeranyl group to the carboxy (C-) terminus targets Rho GTPases to the plasma membrane and promotes their activation by facilitating interaction with guanine nucleotide exchange factors and allowing sequestering by association with guanine dissociation inhibitors. However, it is unclear how these modifications affect neurite extension or how subcellular localization alters signaling from the classical Rho GTPases (RhoA, Rac1, and Cdc42). Here, we review recent data addressing this issue and propose that Rho GTPase geranylgeranylation regulates outgrowth.

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Abbreviations

Arp:

Actin-related protein

ATP:

Adenosine triphosphate

CAAX:

C—cysteine, A—aliphatic amino acid, X—any amino acid

cAMP:

Cyclic adenosine monophosphate

C domain:

Central domain

CNS:

Central nervous system

Cys:

Cysteine

F-actin:

Filamentous actin

FPP:

Farnesyl pyrophosphate

FT:

Farnesyl transferase

G-actin:

Globular actin

GAP:

GTPase activating protein

GDI:

Guanine dissociation inhibitor

GDP:

Guanosine diphosphate

GEF:

Guanine exchange factor

GGOH:

Geranylgeraniol

GGPP:

Geranylgeranyl pyrophosphate

GGT:

Geranylgeranyl transferase

GGTI:

Geranylgeranyl transferase I inhibitor

GTP:

Guanosine triphosphate

GTPases:

Guanine nucleotide triphosphatases

HMG-CoA:

3-Hydroxy-3-methylglutaryl coenzyme A

LIMK:

LIN-11 Islet-1, MEC-3 domain kinase

mDia:

Mammalian diaphanous-related formin

NGF:

Nerve growth factor

N-WASP:

Neuronal Wiskott Aldrich syndrome protein

PAK:

p21-Activated kinase

P domain:

Peripheral domain

ROCK:

Rho-associated coiled-coil-forming protein kinase

WAVE:

WASP family verprolin-homologous protein

References

  1. Strittmatter SM (2002) Modulation of axonal regeneration in neurodegenerative disease: focus on Nogo. J Mol Neurosci 19:117–121

    Article  CAS  PubMed  Google Scholar 

  2. Teter B, Ashford JW (2002) Neuroplasticity in Alzheimer’s disease. J Neurosci Res 70:402–437

    Article  CAS  PubMed  Google Scholar 

  3. Di Giovanni S (2009) Molecular targets for axon regeneration: focus on the intrinsic pathways. Expert Opin Ther Targets 13:1387–1398

    Article  PubMed  Google Scholar 

  4. Fukata M, Nakagawa M, Kaibuchi K (2003) Roles of Rho-family GTPases in cell polarisation and directional migration. Curr Opin Cell Biol 15:590–597

    Article  CAS  PubMed  Google Scholar 

  5. Michaelson D, Rush M, Philips MR (2003) Intracellular targeting of Rho family GTPases: implications of localization on function. In: Symon M (ed) Rho GTPases. Kluwer Academic, New York, pp 17–31

    Google Scholar 

  6. Tojima T, Ito E (2004) Signal transduction cascades underlying de novo protein synthesis required for neuronal morphogenesis in differentiating neurons. Prog Neurobiol 72:183–193

    Article  CAS  PubMed  Google Scholar 

  7. Korobova F, Svitkina T (2008) Arp2/3 complex is important for filopodia formation, growth cone motility, and neuritogenesis in neuronal cells. Mol Biol Cell 19:1561–1574

    Article  CAS  PubMed  Google Scholar 

  8. Da Silva JS, Medina M, Zuliani C, Di Nardo A, Witke W, Dotti CG (2003) RhoA/ROCK regulation of neuritogenesis via profilin IIa-mediated control of actin stability. J Cell Biol 162:1267–1279

    Article  PubMed  Google Scholar 

  9. Gallo G, Letourneau PC (2004) Regulation of growth cone actin filaments by guidance cues. J Neurobiol 58:92–102

    Article  CAS  PubMed  Google Scholar 

  10. Mallavarapu A, Mitchison T (1999) Regulated actin cytoskeleton assembly at filopodium tips controls their extension and retraction. J Cell Biol 146:1097–1106

    Article  CAS  PubMed  Google Scholar 

  11. Nozumi M, Nakagawa H, Miki H, Takenawa T, Miyamoto S (2003) Differential localization of WAVE isoforms in filopodia and lamellipodia of the neuronal growth cone. J Cell Sci 116:239–246

    Article  CAS  PubMed  Google Scholar 

  12. Dent EW, Kalil K (2001) Axon branching requires interactions between dynamic microtubules and actin filaments. J Neurosci 21:9757–9769

    CAS  PubMed  Google Scholar 

  13. Kalil K, Szebenyi G, Dent EW (2000) Common mechanisms underlying growth cone guidance and axon branching. J Neurobiol 44:145–158

    Article  CAS  PubMed  Google Scholar 

  14. Mingorance-Le Meur A, O’Connor TP (2009) Neurite consolidation is an active process requiring constant repression of protrusive activity. EMBO J 28:248–260

    Article  CAS  PubMed  Google Scholar 

  15. Koh CG (2006) Rho GTPases and their regulators in neuronal functions and development. Neurosignals 15:228–237

    Article  CAS  PubMed  Google Scholar 

  16. de Curtis I (2008) Functions of Rac GTPases during neuronal development. Dev Neurosci 30:47–58

    Article  PubMed  Google Scholar 

  17. Bromberg KD, Iyengar R, He JC (2008) Regulation of neurite outgrowth by Gi/o signaling pathways. Front Biosci 13:4544–4557

    Article  CAS  PubMed  Google Scholar 

  18. Witte H, Bradke F (2008) The role of the cytoskeleton during neuronal polarization. Curr Opin Neurobiol 18:479–487

    Article  CAS  PubMed  Google Scholar 

  19. Etienne-Manneville S, Hall A (2002) Rho GTPases in cell biology. Nature 420:629–635

    Article  CAS  PubMed  Google Scholar 

  20. Chen Z, Sun J, Pradines A, Favre G, Adnane J, Sebti SM (2000) Both farnesylated and geranylgeranylated RhoB inhibit malignant transformation and suppress human tumor growth in nude mice. J Biol Chem 275(24):17974–17978

    Article  CAS  PubMed  Google Scholar 

  21. Didsbury JR, Uhing RJ, Snyderman R (1990) Isoprenylation of the low molecular mass GTP-binding proteins Rac1 and Rac2: possible role in membrane localization. Biochem Biophys Res Commun 171:804–812

    Article  CAS  PubMed  Google Scholar 

  22. Rossman KL, Der CJ, Sondek J (2005) GEF means go: turning on Rho GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol 6:167–180

    Article  CAS  PubMed  Google Scholar 

  23. Bishop AL, Hall A (2000) Rho GTPases and their effector proteins. Biochem J 348(Pt 2):241–255

    Article  CAS  PubMed  Google Scholar 

  24. Rohatgi R, Ho HY, Kirschner MW (2000) Mechanism of N-WASP activation by Cdc42 and phosphatidylinositol 4, 5-bisphosphate. J Cell Biol 150:1299–1310

    Article  CAS  PubMed  Google Scholar 

  25. Rohatgi R, Ma L, Miki H, Lopez M, Kirchhausen T, Takenawa T, Kirschner MW (1999) The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly. Cell 97:221–231

    Article  CAS  PubMed  Google Scholar 

  26. Chesarone MA, Goode BL (2009) Actin nucleation and elongation factors: mechanisms and interplay. Curr Opin Cell Biol 21:28–37

    Article  CAS  PubMed  Google Scholar 

  27. Lammers M, Meyer S, Kuhlmann D, Wittinghofer A (2008) Specificity of interactions between mDia isoforms and Rho proteins. J Biol Chem 283:35236–35246

    Article  CAS  PubMed  Google Scholar 

  28. del Pozo MA, Price LS, Alderson NB, Ren XD, Schwartz MA (2000) Adhesion to the extracellular matrix regulates the coupling of the small GTPase Rac to its effector PAK. EMBO J 19:2008–2014

    Article  PubMed  Google Scholar 

  29. Pilpel Y, Segal M (2005) Rapid WAVE dynamics in dendritic spines of cultured hippocampal neurons is mediated by actin polymerization. J Neurochem 95:1401–1410

    Article  CAS  PubMed  Google Scholar 

  30. Higashida C, Miyoshi T, Fujita A, Oceguera-Yanez F, Monypenny J, Andou Y, Narumiya S, Watanabe N (2004) Actin polymerization-driven molecular movement of mDia1 in living cells. Science 303:2007–2010

    Article  CAS  PubMed  Google Scholar 

  31. Suetsugu S, Miki H, Yamaguchi H, Obinata T, Takenawa T (2001) Enhancement of branching efficiency by the actin filament-binding activity of N-WASP/WAVE2. J Cell Sci 114:4533–4542

    CAS  PubMed  Google Scholar 

  32. Luo L, Jan L, Jan YN (1996) Small GTPases in axon outgrowth. Perspect Dev Neurobiol 4:199–204

    CAS  PubMed  Google Scholar 

  33. Nusser N, Gosmanova E, Zheng Y, Tigyi G (2002) Nerve growth factor signals through trkA, phosphatidylinositol 3-kinase, and Rac1 to inactivate Rhoa during the initiation of neuronal differentiation of PC12 cells. J Biol Chem 277:35840–35846

    Article  CAS  PubMed  Google Scholar 

  34. Kranenburg O, Poland M, Gebbink M, Oomen L, Moolenaar WH (1997) Dissociation of LPA-induced cytoskeletal contraction from stress fiber formation by differential localization of RhoA. J Cell Sci 110:2417–2427

    CAS  PubMed  Google Scholar 

  35. Ahnert-Hilger G, Holtje M, Grosse G, Pickert G, Mucke C, Nixdorf-Bergweiler B, Boquet P, Hofmann F, Just I (2004) Differential effects of Rho GTPases on axonal and dendritic development in hippocampal neurones. J Neurochem 90:9–18

    Article  CAS  PubMed  Google Scholar 

  36. Aizawa H, Wakatsuki S, Ishii A, Moriyama K, Sasaki Y, Ohashi K, Sekine-Aizawa Y, Sehara-Fujisawa A, Mizuno K, Goshima Y, Yahara I (2001) Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse. Nat Neurosci 4:367–373

    Article  CAS  PubMed  Google Scholar 

  37. Hirose M, Ishizaki T, Watanabe N, Uehata M, Kranenburg O, Moolenaar WH, Matsumura F, Maekawa M, Bito H, Narumiya S (1998) Molecular dissection of the Rho-associated protein kinase (p160ROCK)-regulated neurite remodeling in neuroblastoma N1E-115 cells. J Cell Biol 141:1625–1636

    Article  CAS  PubMed  Google Scholar 

  38. Bito H, Furuyashiki T, Ishihara H, Shibasaki Y, Ohashi K, Mizuno K, Maekawa M, Ishizaki T, Narumiya S (2000) A critical role for a Rho-associated kinase, p160ROCK, in determining axon outgrowth in mammalian CNS neurons. Neuron 26:431–441

    Article  CAS  PubMed  Google Scholar 

  39. Fournier AE, Takizawa BT, Strittmatter SM (2003) Rho kinase inhibition enhances axonal regeneration in the injured CNS. J Neurosci 23:1416–1423

    CAS  PubMed  Google Scholar 

  40. Marler KJ, Kozma R, Ahmed S, Dong JM, Hall C, Lim L (2005) Outgrowth of neurites from N1E-115 neuroblastoma cells is prevented on repulsive substrates through the action of PAK. Mol Cell Biol 25:5226–5241

    Article  CAS  PubMed  Google Scholar 

  41. Li X, Gao X, Liu G, Xiong W, Wu J, Rao Y (2008) Netrin signal transduction and the guanine nucleotide exchange factor DOCK180 in attractive signaling. Nat Neurosci 11:28–35

    Article  CAS  PubMed  Google Scholar 

  42. Matsuo N, Terao M, Nabeshima Y, Hoshino M (2003) Roles of STEF/TIAM1, guanine nucleotide exchange factors for Rac1, in regulation of growth cone morphology. Mol Cell Neurosci 24:69–81

    Article  CAS  PubMed  Google Scholar 

  43. Ng J, Nardine T, Harms M, Tzu J, Goldstein A, Sun Y, Dietzl G, Dickson BJ, Luo L (2002) Rac GTPases control axon growth, guidance and branching. Nature 416:442–447

    Article  CAS  PubMed  Google Scholar 

  44. Brown MD, Cornejo BJ, Kuhn TB, Bamburg JR (2000) Cdc42 stimulates neurite outgrowth and formation of growth cone filopodia and lamellipodia. J Neurobiol 43:352–364

    Article  CAS  PubMed  Google Scholar 

  45. Garvalov BK, Flynn KC, Neukirchen D, Meyn L, Teusch N, Wu X, Brakebusch C, Bamburg JR, Bradke F (2007) Cdc42 regulates cofilin during the establishment of neuronal polarity. J Neurosci 27:13117–13129

    Article  CAS  PubMed  Google Scholar 

  46. Woo S, Gomez TM (2006) Rac1 and RhoA promote neurite outgrowth through formation and stabilization of growth cone point contacts. J Neurosci 26:1418–1428

    Article  CAS  PubMed  Google Scholar 

  47. Picard M, Petrie RJ, Antoine-Bertrand J, Saint-Cyr-Proulx E, Villemure JF, Lamarche-Vane N (2009) Spatial and temporal activation of the small GTPases RhoA and Rac1 by the netrin-1 receptor UNC5a during neurite outgrowth. Cell Signal 21:1961–1973

    Article  CAS  PubMed  Google Scholar 

  48. Bito H (2003) Dynamic control of neuronal morphogenesis by Rho signaling. J Biochem 134:315–319

    Article  CAS  PubMed  Google Scholar 

  49. Nakamura T, Aoki K, Matsuda M (2005) FRET imaging in nerve growth cones reveals a high level of Rhoa activity within the peripheral domain. Brain Res Mol Brain Res 139:277–287

    Article  CAS  PubMed  Google Scholar 

  50. Kuhn TB, Brown MD, Wilcox CL, Raper JA, Bamburg JR (1999) Myelin and collapsin-1 induce motor neuron growth cone collapse through different pathways: inhibition of collapse by opposing mutants of Rac1. J Neurosci 19:1965–1975

    CAS  PubMed  Google Scholar 

  51. Jin Z, Strittmatter SM (1997) Rac1 mediates collapsin-1-induced growth cone collapse. J Neurosci 17:6256–6263

    CAS  PubMed  Google Scholar 

  52. Sebok A, Nusser N, Debreceni B, Guo Z, Santos MF, Szeberenyi J, Tigyi G (1999) Different roles for RhoA during neurite initiation, elongation, and regeneration in PC12 cells. J Neurochem 73:949–960

    Article  CAS  PubMed  Google Scholar 

  53. Zhang FL, Casey PJ (1996) Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem 65:241–269

    Article  CAS  PubMed  Google Scholar 

  54. Fenton RG, Kung HF, Longo DL, Smith MR (1992) Regulation of intracellular actin polymerization by prenylated cellular proteins. J Cell Biol 117:347–356

    Article  CAS  PubMed  Google Scholar 

  55. Stancu C, Sima A (2001) Statins: mechanism of action and effects. J Cell Mol Med 5:378–387

    Article  CAS  PubMed  Google Scholar 

  56. Kinsella BT, Erdman RA, Maltese WA (1991) Posttranslational modification of HA-Ras p21 by farnesyl versus geranylgeranyl isoprenoids is determined by the COOH-terminal amino acid. Proc Natl Acad Sci USA 88(20):8934–8938

    Article  CAS  PubMed  Google Scholar 

  57. Backlund PS Jr (1997) Post-translational processing of RhoA. Carboxyl methylation of the carboxyl-terminal prenylcysteine increases the half-life of RhoA. J Biol Chem 272:33175–33180

    Article  CAS  PubMed  Google Scholar 

  58. Molnar G, Dagher MC, Geiszt M, Settleman J, Ligeti E (2001) Role of prenylation in the interaction of Rho-family small GTPases with GTPase activating proteins. Biochemistry 40:10542–10549

    Article  CAS  PubMed  Google Scholar 

  59. Crick DC, Andres DA, Danesi R, Macchia M, Waechter CJ (1998) Geranylgeraniol overcomes the block of cell proliferation by lovastatin in C6 glioma cells. J Neurochem 70:2397–2405

    Article  CAS  PubMed  Google Scholar 

  60. Zhong WB, Liang YC, Wang CY, Chang TC, Lee WS (2005) Lovastatin suppresses invasiveness of anaplastic thyroid cancer cells by inhibiting Rho geranylgeranylation and Rhoa/ROCK signaling. Endocr Relat Cancer 12:615–629

    Article  CAS  PubMed  Google Scholar 

  61. Ko M, Zou K, Minagawa H, Yu W, Gong JS, Yanagisawa K, Michikawa M (2005) Cholesterol-mediated neurite outgrowth is differently regulated between cortical and hippocampal neurons. J Biol Chem 280:42759–42765

    Article  CAS  PubMed  Google Scholar 

  62. Fan QW, Yu W, Gong JS, Zou K, Sawamura N, Senda T, Yanagisawa K, Michikawa M (2002) Cholesterol-dependent modulation of dendrite outgrowth and microtubule stability in cultured neurons. J Neurochem 80:178–190

    Article  CAS  PubMed  Google Scholar 

  63. Fernandez-Hernando C, Suarez Y, Lasuncion MA (2005) Lovastatin-induced PC-12 cell differentiation is associated with Rhoa/RhoA kinase pathway inactivation. Mol Cell Neurosci 29:591–602

    Article  CAS  PubMed  Google Scholar 

  64. Holmberg E, Nordstrom T, Gross M, Kluge B, Zhang SX, Doolen S (2006) Simvastatin promotes neurite outgrowth in the presence of inhibitory molecules found in central nervous system injury. J Neurotrauma 23:1366–1378

    Article  PubMed  Google Scholar 

  65. Pooler AM, Xi SC, Wurtman RJ (2006) The 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor pravastatin enhances neurite outgrowth in hippocampal neurons. J Neurochem 97:716–723

    Article  CAS  PubMed  Google Scholar 

  66. Evangelopoulos ME, Weis J, Kruttgen A (2009) Mevastatin-induced neurite outgrowth of neuroblastoma cells via activation of EGFR. J Neurosci Res 87:2138–2144

    Article  CAS  PubMed  Google Scholar 

  67. Evangelopoulos ME, Wuller S, Weis J, Kruttgen A (2010) A role of nitric oxide in neurite outgrowth of neuroblastoma cells triggered by mevastatin or serum reduction. Neurosci Lett 468:28–33

    Article  CAS  PubMed  Google Scholar 

  68. Nusse O, Neer EJ (1996) Localization of Gα0 to growth cones in PC12 cells: role of Gα0 association with receptors and Gβγ. J Cell Sci 109(Pt 1):221–228

    PubMed  Google Scholar 

  69. Sano M, Sato-Suzuki I, Fujita H, Morita I, Nagao M, Murota S (1998) NO is not involved in the simvastatin induced cell division and differentiation in PC12 cells. Neurosci Lett 243:73–76

    Article  CAS  PubMed  Google Scholar 

  70. Sato-Suzuki I, Murota S (1996) Simvastatin inhibits the division and induces neurite-like outgrowth in PC12 cells. Neurosci Lett 220:21–24

    Article  CAS  PubMed  Google Scholar 

  71. Zhou XP, Wu KY, Liang B, Fu XQ, Luo ZG (2008) TrkB-mediated activation of geranylgeranyltransferase I promotes dendritic morphogenesis. Proc Natl Acad Sci USA 105:17181–17186

    Article  CAS  PubMed  Google Scholar 

  72. Schulz JG, Bosel J, Stoeckel M, Megow D, Dirnagl U, Endres M (2004) HMG-CoA reductase inhibition causes neurite loss by interfering with geranylgeranylpyrophosphate synthesis. J Neurochem 89:24–32

    Article  CAS  PubMed  Google Scholar 

  73. Kim WY, Gonsiorek EA, Barnhart C, Davare MA, Engebose AJ, Lauridsen H, Bruun D, Lesiak A, Wayman G, Bucelli R, Higgins D, Lein PJ (2009) Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation. J Neurochem 108:1057–1071

    Article  CAS  PubMed  Google Scholar 

  74. Maltese WA, Sheridan KM (1985) Differentiation of neuroblastoma cells induced by an inhibitor of mevalonate synthesis: relation of neurite outgrowth and acetylcholinesterase activity to changes in cell proliferation and blocked isoprenoid synthesis. J Cell Physiol 125:540–558

    Article  CAS  PubMed  Google Scholar 

  75. Daglioglu E, Berker M, Demirci M, Tuncel M, Karabulut E, Tuncel A (2010) Microscopic and electrophysiological changes on regenerating sciatic nerves of rats treated with simvastatin. Folia Neuropathol 48:49–56

    CAS  PubMed  Google Scholar 

  76. Wu KY, Zhou XP, Luo ZG (2010) Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells. Mol Brain 3:18

    Article  PubMed  Google Scholar 

  77. Kinsella BT, Erdman RA, Maltese WA (1991) Carboxyl-terminal isoprenylation of Ras-related GTP-binding proteins encoded by Rac1, Rac2, and RalA. J Biol Chem 266:9786–9794

    CAS  PubMed  Google Scholar 

  78. Wherlock M, Mellor H (2002) The Rho GTPase family: a Racs to Wrchs story. J Cell Sci 115:239–240

    CAS  PubMed  Google Scholar 

  79. Mazieres J, Tillement V, Allal C, Clanet C, Bobin L, Chen Z, Sebti SM, Favre G, Pradines A (2005) Geranylgeranylated, but not farnesylated, RhoB suppresses Ras transformation of NIH-3T3 cells. Exp Cell Res 304(2):354–364

    Article  CAS  PubMed  Google Scholar 

  80. Solski PA, Helms W, Keely PJ, Su L, Der CJ (2002) RhoA biological activity is dependent on prenylation but independent of specific isoprenoid modification. Cell Growth Differ 13(8):363–373

    CAS  PubMed  Google Scholar 

  81. Rolfe BE, Worth NF, World CJ, Campbell JH, Campbell GR (2005) Rho and vascular disease. Atherosclerosis 183:1–16

    Article  CAS  PubMed  Google Scholar 

  82. Roberts PJ, Mitin N, Keller PJ, Chenette EJ, Madigan JP, Currin RO, Cox AD, Wilson O, Kirschmeier P, Der CJ (2008) Rho family GTPase modification and dependence on CAAX motif-signaled posttranslational modification. J Biol Chem 283:25150–25163

    Article  CAS  PubMed  Google Scholar 

  83. Allal C, Favre G, Couderc B, Salicio S, Sixou S, Hamilton AD, Sebti SM, Lajoie-Mazenc I, Pradines A (2000) RhoA prenylation is required for promotion of cell growth and transformation and cytoskeleton organization but not for induction of serum response element transcription. J Biol Chem 275:31001–31008

    Article  CAS  PubMed  Google Scholar 

  84. Robbe K, Otto-Bruc A, Chardin P, Antonny B (2003) Dissociation of GDP dissociation inhibitor and membrane translocation are required for efficient activation of Rac by the Dbl homology–pleckstrin homology region of TIAM. J Biol Chem 278:4756–4762

    Article  CAS  PubMed  Google Scholar 

  85. Dunford JE, Rogers MJ, Ebetino FH, Phipps RJ, Coxon FP (2006) Inhibition of protein prenylation by bisphosphonates causes sustained activation of Rac, Cdc42, and Rho GTPases. J Bone Miner Res 21(5):684–694

    Article  PubMed  Google Scholar 

  86. Jacobson JR, Dudek SM, Birukov KG, Ye SQ, Grigoryev DN, Girgis RE, Garcia JG (2004) Cytoskeletal activation and altered gene expression in endothelial barrier regulation by simvastatin. Am J Respir Cell Mol Biol 30:662–670

    Article  CAS  PubMed  Google Scholar 

  87. Hoffman GR, Nassar N, Cerione RA (2000) Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI. Cell 100:345–356

    Article  CAS  PubMed  Google Scholar 

  88. DerMardirossian C, Bokoch GM (2005) GDIs: central regulatory molecules in Rho GTPase activation. Trends Cell Biol 15:356–363

    Article  CAS  PubMed  Google Scholar 

  89. Dovas A, Couchman JR (2005) RhoGDI: multiple functions in the regulation of Rho family GTPase activities. Biochem J 390:1–9

    Article  CAS  PubMed  Google Scholar 

  90. Moissoglu K, Slepchenko BM, Meller N, Horwitz AF, Schwartz MA (2006) In vivo dynamics of Rac-membrane interactions. Mol Biol Cell 17:2770–2779

    Article  CAS  PubMed  Google Scholar 

  91. Faure J, Dagher MC (2001) Interactions between Rho GTPases and Rho GDP dissociation inhibitor (Rho-GDI). Biochimie 83:409–414

    Article  CAS  PubMed  Google Scholar 

  92. Hancock JF, Hall A (1993) A novel role for RhoGDI as an inhibitor of GAP proteins. EMBO J 12:1915–1921

    CAS  PubMed  Google Scholar 

  93. Ligeti E, Dagher MC, Hernandez SE, Koleske AJ, Settleman J (2004) Phospholipids can switch the GTPase substrate preference of a GTPase-activating protein. J Biol Chem 279:5055–5058

    Article  CAS  PubMed  Google Scholar 

  94. Miyazaki K, Komatsu S, Ikebe M (2006) Dynamics of RhoA and ROKα translocation in single living cells. Cell Biochem Biophys 45:243–254

    Article  CAS  PubMed  Google Scholar 

  95. Montani L, Gerrits B, Gehrig P, Kempf A, Dimou L, Wollscheid B, Schwab ME (2009) Neuronal NOGO-A modulates growth cone motility via Rho-GTP/limkLIMK1/cofilin in the unlesioned adult nervous system. J Biol Chem 284:10793–10807

    Article  CAS  PubMed  Google Scholar 

  96. Gungabissoon RA, Bamburg JR (2003) Regulation of growth cone actin dynamics by ADF/cofilin. J Histochem Cytochem 51:411–420

    CAS  PubMed  Google Scholar 

  97. Tcherkezian J, Lamarche-Vane N (2007) Current knowledge of the large RhoGAP family of proteins. Biol Cell 99:67–86

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the TWU Department of Biology, Chancellor’s Research Fellows Awards, Summer Stipend Awards, Closing the GAPs, and grants from the TWU Research Enhancement Program.

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  1. Department of Biology, Texas Woman’s University, PO Box 425799, Denton, TX, 46204-5799, USA

    Filsy Samuel & DiAnna L. Hynds

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Correspondence to DiAnna L. Hynds.

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Samuel, F., Hynds, D.L. RHO GTPase Signaling for Axon Extension: Is Prenylation Important?. Mol Neurobiol 42, 133–142 (2010). https://doi.org/10.1007/s12035-010-8144-2

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