Rap1 GTPase Activation and Barrier Enhancement in RPE Inhibits Choroidal Neovascularization In Vivo

PLoS ONE

Volumn 8, Issue 9, 2013, Pages

  Wittchen, Erika S ^a   Nishimura, Eiichi ^b,e   McCloskey, Manabu ^b   Wang, Haibo ^b   Quilliam, Lawrence A ^c   Chrzanowska Wodnicka, Magdalena ^d   Hartnett, M Elizabeth ^b  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^c INDIANA UNIVERSITY   (United States)

^d BLOOD RESEARCH INSTITUTE   (United States)

^e SHOWA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

BETA CATENIN; F ACTIN; PROTEIN ZO1; RAP1 PROTEIN; SHORT HAIRPIN RNA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CELL ADHESION; CELL JUNCTION; CONTROLLED STUDY; ENZYME ACTIVATION; HUMAN; HUMAN CELL; IN VIVO STUDY; MOUSE; NONHUMAN; PATHOGENESIS; PIGMENT EPITHELIUM; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN LOCALIZATION; RETINA MACULA DEGENERATION; SUBRETINAL NEOVASCULARIZATION;

ANIMALS; BLOOD-RETINAL BARRIER; CHOROIDAL NEOVASCULARIZATION; CYCLIC AMP; DISEASE MODELS, ANIMAL; ENDOTHELIAL CELLS; ENZYME ACTIVATION; HUMANS; INTERCELLULAR JUNCTIONS; MACULAR DEGENERATION; MICE; MICE, KNOCKOUT; RAP1 GTP-BINDING PROTEINS; TRANSENDOTHELIAL AND TRANSEPITHELIAL MIGRATION;

EID: 84883828886     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0073070     Document Type: Article

References (75)

1. Hartsock A, Nelson WJ, (2008) Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta 1778: 660-669.
2. Spindler V, Schlegel N, Waschke J, (2010) Role of GTPases in control of microvascular permeability. Cardiovasc Res 87: 243-253.
3. Terry S, Nie M, Matter K, Balda MS, (2010) Rho signaling and tight junction functions. Physiology (Bethesda) 25: 16-26.
4. Hall A, (1998) Rho GTPases and the Actin Cytoskeleton. Science 279: 509-514.
5. Zwartkruis FJ, Bos JL (1999) Ras and Rap1: two highly related small GTPases with distinct function. Exp Cell Res. 157-165.
6. Boettner B, Van Aelst L, (2009) Control of cell adhesion dynamics by Rap1 signaling. Curr Opin Cell Biol 21: 684-693.
7. Price LS, Hajdo-Milasinovic A, Zhao J, Zwartkruis FJ, Collard JG, et al. (2004) Rap1 regulates E-cadherin-mediated cell-cell adhesion. J Biol Chem 279: 35127-35132.
8. Hogan C, Serpente N, Cogram P, Hosking CR, Bialucha CU, et al. (2004) Rap1 regulates the formation of E-cadherin-based cell-cell contacts. Mol Cell Biol. 6690-6700.
9. Wittchen ES, Worthylake RA, Kelly P, Casey PJ, Quilliam LA, et al. (2005) Rap1 GTPase inhibits leukocyte transmigration by promoting endothelial barrier function. J Biol Chem 280: 11675-11682.
10. Cullere X, Shaw SK, Andersson L, Hirahashi J, Luscinskas FW, et al. (2005) Regulation of vascular endothelial barrier function by Epac, a cAMP-activated exchange factor for Rap GTPase. Blood 105: 1950-1955.
11. Fukuhara S, Sakurai A, Yamagishi A, Sako K, Mochizuki N, (2006) Vascular endothelial cadherin-mediated cell-cell adhesion regulated by a small GTPase, Rap1. J Biochem Mol Biol 39: 132-139.
12. Birukova AA, Fu P, Xing J, Birukov KG, (2009) Rap1 mediates protective effects of iloprost against ventilator-induced lung injury. J Appl Physiol 107: 1900-1910.
13. Wittchen ES, Aghajanian A, Burridge K, (2011) Isoform-specific differences between Rap1A and Rap1B GTPases in the formation of endothelial cell junctions. Small GTPases 2: 65-76.
14. Chrzanowska-Wodnicka M, Smyth SS, Schoenwaelder SM, Fischer TH, White GC 2nd, (2005) Rap1b is required for normal platelet function and hemostasis in mice. J Clin Invest 115: 680-687.
15. Li Y, Yan J, De P, Chang HC, Yamauchi A, et al. (2007) Rap1a null mice have altered myeloid cell functions suggesting distinct roles for the closely related Rap1a and 1b proteins. J Immunol 179: 8322-8331.
16. Chrzanowska-Wodnicka M, (2010) Regulation of angiogenesis by a small GTPase Rap1. Vascul Pharmacol 53: 1-10.
17. Duchniewicz M, Zemojtel T, Kolanczyk M, Grossmann S, Scheele JS, et al. (2006) Rap1A-deficient T and B cells show impaired integrin-mediated cell adhesion. Mol Cell Biol 26: 643-653.
18. Wang H, Wittchen ES, Hartnett ME, (2011) Breaking barriers: insight into the pathogenesis of neovascular age-related macular degeneration. Eye and Brain 3: 19-28.
19. Christoforidis JB, Tecce N, Dell'Omo R, Mastropasqua R, Verolino M, et al. (2011) Age related macular degeneration and visual disability. Curr Drug Targets 12: 221-233.
20. Catt Research Group, Martin DF, Maguire MG, Ying GS, Grunwald JE, et al (2011) Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 364: 1897-1908.
21. Nishijima K, Ng Y-S, Zhong L, Bradley J, Schubert W, et al. (2007) Vascular Endothelial Growth Factor-A Is a Survival Factor for Retinal Neurons and a Critical Neuroprotectant during the Adaptive Response to Ischemic Injury. The American Journal of Pathology 171: 53-67.
22. Saint-Geniez M, Kurihara T, Sekiyama E, Maldonado AE, D'Amore PA, (2009) An essential role for RPE-derived soluble VEGF in the maintenance of the choriocapillaris. Proc Natl Acad Sci U S A 106: 18751-18756.
23. Geisen P, McColm JR, Hartnett ME, (2006) Choroidal endothelial cells transmigrate across the retinal pigment epithelium but do not proliferate in response to soluble vascular endothelial growth factor. Exp Eye Res 82: 608-619.
24. Geisen P, McColm JR, King BM, Hartnett ME, (2006) Characterization of barrier properties and inducible VEGF expression of several types of retinal pigment epithelium in medium-term culture. Curr Eye Res 31: 739-748.
25. Martinez-Palomo A, Meza I, Beaty G, Cereijido M, (1980) Experimental modulation of occluding junctions in a cultured transporting epithelium. J Cell Biol 87: 736-745.
26. Wittchen ES, Hartnett ME, (2011) The small GTPase Rap1 is a novel regulator of RPE cell barrier function. Invest Ophthalmol Vis Sci 52: 7455-7463.
27. Atienza JM, Yu N, Kirstein SL, Xi B, Wang X, et al. (2006) Dynamic and Label-Free Cell-Based Assays Using the Real-Time Cell Electronic Sensing System. Assay and Drug Development Technologies 4: 597-607.
28. Solly K, Wang X, Xu X, Strulovici B, Zheng W, (2004) Application of real-time cell electronic sensing (RT-CES) technology to cell-based assays. Assay Drug Dev Technol 2: 363-372.
29. Yan J, Li F, Ingram DA, Quilliam LA, (2008) Rap1a is a key regulator of fibroblast growth factor 2-induced angiogenesis and together with Rap1b controls human endothelial cell functions. Mol Cell Biol 28: 5803-5810.
30. Grossniklaus HE, Kang SJ, Berglin L, (2010) Animal models of choroidal and retinal neovascularization. Prog Retin Eye Res 29: 500-519.
31. Kitt KN, Nelson WJ, (2011) Rapid suppression of activated Rac1 by cadherins and nectins during de novo cell-cell adhesion. PLoS One 6: e17841.
32. Enserink JM, Christensen AE, de Rooij J, van Triest M, Schwede F, et al. (2002) A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK. Nat Cell Biol 4: 901-906.
33. Otani T, Ichii T, Aono S, Takeichi M, (2006) Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells. The Journal of Cell Biology 175: 135-146.
34. Monaghan-Benson E, Hartmann J, Vendrov AE, Budd S, Byfield G, et al. (2010) The role of vascular endothelial growth factor-induced activation of NADPH oxidase in choroidal endothelial cells and choroidal neovascularization. Am J Pathol 177: 2091-2102.
35. Fukuhara S, Sakurai A, Sano H, Yamagishi A, Somekawa S, et al. (2005) Cyclic AMP potentiates vascular endothelial cadherin-mediated cell-cell contact to enhance endothelial barrier function through an Epac-Rap1 signaling pathway. Mol Cell Biol 25: 136-146.
36. Noda K, Zhang J, Fukuhara S, Kunimoto S, Yoshimura M, et al. (2010) Vascular endothelial-cadherin stabilizes at cell-cell junctions by anchoring to circumferential actin bundles through alpha- and beta-catenins in cyclic AMP-Epac-Rap1 signal-activated endothelial cells. Mol Biol Cell 21: 584-596.
37. Kooistra MR, Corada M, Dejana E, Bos JL, (2005) Epac1 regulates integrity of endothelial cell junctions through VE-cadherin. FEBS Lett 579: 4966-4972.
38. Birukova AA, Burdette D, Moldobaeva N, Xing J, Fu P, et al. (2010) Rac GTPase is a hub for protein kinase A and Epac signaling in endothelial barrier protection by cAMP. Microvasc Res 79: 128-138.
39. Peterson LJ, Wittchen ES, Geisen P, Burridge K, Hartnett ME, (2007) Heterotypic RPE-choroidal endothelial cell contact increases choroidal endothelial cell transmigration via PI 3-kinase and Rac1. Exp Eye Res 84: 737-744.
40. Geisen P, Peterson LJ, Martiniuk D, Uppal A, Saito Y, et al. (2008) Neutralizing antibody to VEGF reduces intravitreous neovascularization and may not interfere with ongoing intraretinal vascularization in a rat model of retinopathy of prematurity. Mol Vis 14: 345-357.
41. Tawa H, Rikitake Y, Takahashi M, Amano H, Miyata M, et al. (2010) Role of Afadin in Vascular Endothelial Growth Factor- and Sphingosine 1-Phosphate-Induced Angiogenesis. Circ Res 106: 1731-1742.
42. McLachlan RW, Yap AS, (2010) Protein tyrosine phosphatase activity is necessary for E-cadherin-activated Src signaling. Cytoskeleton (Hoboken) 68: 32-43.
43. Takeda A, Baffi JZ, Kleinman ME, Cho WG, Nozaki M, et al. (2009) CCR3 is a target for age-related macular degeneration diagnosis and therapy. Nature 460: 225-230.
44. Wang H, Geisen P, Wittchen ES, King B, Burridge K, et al. (2011) The role of RPE cell-associated VEGF(1)(8)(9) in choroidal endothelial cell transmigration across the RPE. Invest Ophthalmol Vis Sci 52: 570-578.
45. Xu J, Zhu D, Sonoda S, He S, Spee C,et al. Over-expression of BMP4 inhibits experimental choroidal neovascularization by modulating VEGF and MMP-9. Angiogenesis 15: 213-227.
46. Shi X, Semkova I, Muther PS, Dell S, Kociok N, et al. (2006) Inhibition of TNF-alpha reduces laser-induced choroidal neovascularization. Exp Eye Res 83: 1325-1334.
47. Ambati J, (2011) Age-related macular degeneration and the other double helix. The Cogan Lecture. Invest Ophthalmol Vis Sci 52: 2165-2169.
48. Giani A, Thanos A, Roh MI, Connolly E, Trichonas G, et al. (2011) In Vivo Evaluation of Laser-Induced Choroidal Neovascularization Using Spectral-Domain Optical Coherence Tomography. Investigative Ophthalmology & Visual Science 52: 3880-3887.
49. Miller H, Miller B, Ryan SJ, (1986) The role of retinal pigment epithelium in the involution of subretinal neovascularization. Investigative Ophthalmology & Visual Science 27: 1644-1652.
50. Severson EA, Lee WY, Capaldo CT, Nusrat A, Parkos CA, (2009) Junctional adhesion molecule A interacts with Afadin and PDZ-GEF2 to activate Rap1A, regulate beta1 integrin levels, and enhance cell migration. Mol Biol Cell 20: 1916-1925.
51. Carmona G, Gottig S, Orlandi A, Scheele J, Bauerle T, et al. (2009) Role of the small GTPase Rap1 for integrin activity regulation in endothelial cells and angiogenesis. Blood 113: 488-497.
52. Chrzanowska-Wodnicka M, Kraus AE, Gale D, White GC 2nd, Vansluys J, (2008) Defective angiogenesis, endothelial migration, proliferation, and MAPK signaling in Rap1b-deficient mice. Blood 111: 2647-2656.
53. Lakshmikanthan S, Sobczak M, Chun C, Henschel A, Dargatz J, et al. (2011) Rap1 promotes VEGFR2 activation and angiogenesis by a mechanism involving integrin alphavbeta(3). Blood 118: 2015-2026.
54. Adamson RH, Ly JC, Sarai RK, Lenz JF, Altangerel A, et al. (2008) Epac/Rap1 pathway regulates microvascular hyperpermeability induced by PAF in rat mesentery. Am J Physiol Heart Circ Physiol 294: H1188-1196.
55. Stokman G, Qin Y, Genieser HG, Schwede F, de Heer E, et al. (2011) Epac-Rap signaling reduces cellular stress and ischemia-induced kidney failure. J Am Soc Nephrol 22: 859-872.
56. Stevens TS, Bressler NM, Maguire MG, Bressler SB, Fine SL, et al. (1997) Occult choroidal neovascularization in age-related macular degeneration: A natural history study. Archives of Ophthalmology 115: 345-350.
57. Arthur WT, Quilliam LA, Cooper JA, (2004) Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors. J Cell Biol 167: 111-122.
58. Birukova AA, Zagranichnaya T, Fu P, Alekseeva E, Chen W, et al. (2007) Prostaglandins PGE(2) and PGI(2) promote endothelial barrier enhancement via PKA- and Epac1/Rap1-dependent Rac activation. Exp Cell Res 313: 2504-2520.
59. Birukova AA, Zagranichnaya T, Alekseeva E, Bokoch GM, Birukov KG (2008) Epac/Rap and PKA are novel mechanisms of ANP-induced Rac-mediated pulmonary endothelial barrier protection. J Cell Physiol.
60. Burridge K, Wennerberg K, (2004) Rho and Rac take center stage. Cell 116: 167-179.
61. Wojciak-Stothard B, Ridley AJ, (2002) Rho GTPases and the regulation of endothelial permeability. Vascul Pharmacol 39: 187-199.
62. Nimnual AS, Taylor LJ, Bar-Sagi D, (2003) Redox-dependent downregulation of Rho by Rac. Nat Cell Biol 5: 236-241.
63. Pannekoek WJ, Kooistra MR, Zwartkruis FJ, Bos JL, (2009) Cell-cell junction formation: the role of Rap1 and Rap1 guanine nucleotide exchange factors. Biochim Biophys Acta 1788: 790-796.
64. Asuri S, Yan J, Paranavitana NC, Quilliam LA, (2008) E-cadherin dis-engagement activates the Rap1 GTPase. J Cell Biochem 105: 1027-1037.
65. Sakurai A, Fukuhara S, Yamagishi A, Sako K, Kamioka Y, et al. (2006) MAGI-1 is required for Rap1 activation upon cell-cell contact and for enhancement of vascular endothelial cadherin-mediated cell adhesion. Mol Biol Cell 17: 966-976.
66. Cunningham KE, Turner JR, (2012) Myosin light chain kinase: pulling the strings of epithelial tight junction function. Ann N Y Acad Sci 1258: 34-42.
67. Ruiz-Loredo AY, Lopez E, Lopez-Colome AM, (2011) Thrombin promotes actin stress fiber formation in RPE through Rho/ROCK-mediated MLC phosphorylation. J Cell Physiol 226: 414-423.
68. Shen L, Black ED, Witkowski ED, Lencer WI, Guerriero V, et al. (2006) Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure. J Cell Sci 119: 2095-2106.
69. Shivanna M, Srinivas SP, (2010) Elevated cAMP opposes (TNF-alpha)-induced loss in the barrier integrity of corneal endothelium. Mol Vis 16: 1781-1790.
70. Srinivas SP, Satpathy M, Gallagher P, Lariviere E, Van Driessche W, (2004) Adenosine induces dephosphorylation of myosin II regulatory light chain in cultured bovine corneal endothelial cells. Exp Eye Res 79: 543-551.
71. Nakajima H, Tanoue T, (2011) Lulu2 regulates the circumferential actomyosin tensile system in epithelial cells through p114RhoGEF. The Journal of Cell Biology 195: 245-261.
72. Hayashi T, Carthew RW, (2004) Surface mechanics mediate pattern formation in the developing retina. Nature 431: 647-652.
73. Boettner B, Van Aelst L, (2007) The Rap GTPase activator Drosophila PDZ-GEF regulates cell shape in epithelial migration and morphogenesis. Mol Cell Biol 27: 7966-7980.
74. O'Keefe DD, Gonzalez-Nino E, Edgar BA, Curtiss J (2012) Discontinuities in Rap1 activity determine epithelial cell morphology within the developing wing of Drosophila. Dev Biol.
75. Shirinifard A, Glazier JA, Swat M, Gens JS, Family F, et al. (2012) Adhesion failures determine the pattern of choroidal neovascularization in the eye: a computer simulation study. PLoS Comput Biol 8: e1002440.