Regulation of signaling interactions and receptor endocytosis in growing blood vessels

Cell Adhesion and Migration

Volumn 8, Issue 4, 2014, Pages 366-377

  Pitulescu, Mara E ^a   Adams, Ralf H ^a  

^a UNIVERSITY OF MÜNSTER   (Germany)

Author keywords

Endocytosis; Endothelial cells; Eph; Ephrin; Mural cells; Receptor

Indexed keywords

CLATHRIN; EPHEDRINE; EPHRIN B2; EPHRIN RECEPTOR B2; EPHRIN RECEPTOR B4; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN TYROSINE KINASE; VASCULOTROPIN; VASCULOTROPIN RECEPTOR; VASCULOTROPIN RECEPTOR 2;

ANGIOGENESIS; ANIMAL CELL; CARDIOVASCULAR SYSTEM; ENDOCYTOSIS; ENDOTHELIUM; FIBROSIS; KIDNEY INJURY; MORPHOGENESIS; NONHUMAN; PROTEIN FUNCTION; PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; VASCULAR SMOOTH MUSCLE; VASCULARIZATION; ANIMAL; BLOOD VESSEL; ENDOTHELIUM CELL; GROWTH, DEVELOPMENT AND AGING; HUMAN; KIDNEY; METABOLISM; MOUSE; NEOVASCULARIZATION (PATHOLOGY); PATHOLOGY; PHYSIOLOGY; ZEBRA FISH;

ANIMALS; BLOOD VESSELS; ENDOCYTOSIS; ENDOTHELIAL CELLS; EPHRIN-B2; FIBROSIS; HUMANS; KIDNEY; MICE; MORPHOGENESIS; NEOVASCULARIZATION, PATHOLOGIC; NEOVASCULARIZATION, PHYSIOLOGIC; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTOR, EPHB4; RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA; SIGNAL TRANSDUCTION; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2; ZEBRAFISH;

EID: 84919922690     PISSN: 19336918     EISSN: 19336926     Source Type: Journal    
DOI: 10.4161/19336918.2014.970010     Document Type: Review

References (151)

1. Risau W, Flamme I. Vasculogenesis. Annu Rev Cell Dev Biol 1995;11:73-91; PMID: 8689573; http://dx. doi.org/10.1146/annurev. cb.11.110195.000445
2. Strilic B, Kucera T, Eglinger J, Hughes MR, McNagny KM, Tsukita S, Dejana E, Ferrara N, Lammert E. The molecular basis of vascular lumen formation in the developing mouse aorta. Dev Cell 2009;17:505-15; PMID: 19853564; http://dx.doi.org/10.1016/j.devcel.2009.08.011
3. Drake CJ, Fleming PA. Vasculogenesis in the day 6.5 to 9.5 mouse embryo. Blood 2000;95:1671-9; PMID: 10688823
4. Gerety SS, Anderson DJ. Cardiovascular ephrinB2 function is essential for embryonic angiogenesis. Development 2002;129:1397-410; PMID: 11880349
5. Herbert SP, Huisken J, Kim TN, Feldman ME, Houseman BT, Wang RA, Shokat KM, Stainier DY. Arterial-venous segregation by selective cell sprouting: an alternative mode of blood vessel formation. Science 2009;326:294-8; PMID: 19815777; http://dx.doi.org/10.1126/science.1178577
6. Lindskog H, Kim YH, Jelin EB, Kong Y, Guevara-Gallardo S, Kim TN, Wang RA. Molecular identification of venous progenitors in the dorsal aorta reveals an aortic origin for the cardinal vein in mammals. Development 2014;141:1120-8; PMID: 24550118; http://dx.doi.org/10.1242/dev. 101808
7. Ruhrberg C, Gerhardt H, Golding M, Watson R, Ioannidou S, Fujisawa H, Betsholtz C, Shima DT. Spatially restricted patterning cues provided by heparinbinding VEGF-A control blood vessel branching morphogenesis. Genes Dev 2002;16:2684-98; PMID: 12381667; http://dx.doi.org/10.1101/gad. 242002
8. Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, Jeltsch M, Mitchell C, Alitalo K, Shima D, et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 2003;161:1163-77; PMID: 12810700; http://dx. doi.org/10.1083/jcb.200302047
9. Phng LK, Stanchi F, Gerhardt H. Filopodia are dispensable for endothelial tip cell guidance. Development 2013;140:4031-40; PMID: 24046319; http://dx.doi.org/10.1242/dev. 097352
10. Jakobsson L, Franco CA, Bentley K, Collins RT, Ponsioen B, Aspalter IM, Rosewell I, Busse M, Thurston G, Medvinsky A, et al. Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting. Nat Cell Biol 2010;12:943-53; PMID: 20871601; http://dx.doi.org/10.1038/ncb2103
11. Bentley K, Franco CA, Philippides A, Blanco R, Dierkes M, Gebala V, Stanchi F, Jones M, Aspalter IM, Cagna G, et al. The role of differential VE-cadherin dynamics in cell rearrangement during angiogenesis. Nat Cell Biol 2014;16:309-21; PMID: 24658686; http://dx.doi.org/10.1038/ncb2926
12. Geudens I, Gerhardt H. Coordinating cell behaviour during blood vessel formation. Development 2011;138:4569-83; PMID: 21965610; http://dx.doi.org/10.1242/dev. 062323
13. Yang Y, Oliver G. Development of the mammalian lymphatic vasculature. J Clin Invest 2014;124:888-97; PMID: 24590273; http://dx.doi.org/10.1172/JCI71609
14. Srinivasan RS, Dillard ME, Lagutin OV, Lin FJ, Tsai S, Tsai MJ, Samokhvalov IM, Oliver G. Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature. Genes Dev 2007;21:2422-32; PMID: 17908929; http://dx.doi.org/10.1101/gad. 1588407
15. Yang Y, Garcia-Verdugo JM, Soriano-Navarro M, Srinivasan RS, Scallan JP, Singh MK, Epstein JA, Oliver G. Lymphatic endothelial progenitors bud from the cardinal vein and intersomitic vessels in mammalian embryos. Blood 2012;120:2340-8; PMID: 22859612; http://dx.doi.org/10.1182/blood-2012-05-428607
16. Hagerling R, Pollmann C, Andreas M, Schmidt C, Nurmi H, Adams RH, Alitalo K, Andresen V, Schulte-Merker S, Kiefer F. A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopy. EMBO J 2013;32:629-44; PMID: 23299940; http://dx.doi.org/10.1038/emboj. 2012.340
17. Adams RH, Alitalo K. Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol 2007;8:464-78; PMID: 17522591; http://dx.doi.org/10.1038/nrm2183
18. Jain RK. Molecular regulation of vessel maturation. Nat Med 2003;9:685-93; PMID: 12778167; http://dx.doi.org/10.1038/nm0603-685
19. Ehling M, Adams S, Benedito R, Adams RH. Notch controls retinal blood vessel maturation and quiescence. Development 2013;140:3051-61; PMID: 23785053; http://dx.doi.org/10.1242/dev. 093351
20. Risau W. Mechanisms of angiogenesis. Nature 1997;386:671-4; PMID: 9109485; http://dx.doi.org/10.1038/386671a0
21. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407:249-57; PMID: 11001068; http://dx.doi.org/10.1038/35025220
22. Potente M, Gerhardt H, Carmeliet P. Basic and therapeutic aspects of angiogenesis. Cell 2011;146:873-87; PMID: 21925313; http://dx.doi.org/10.1016/j. cell.2011.08.039
23. Stacker SA, Williams SP, Karnezis T, Shayan R, Fox SB, Achen MG. Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat Rev Cancer 2014;14:159-72; PMID: 24561443; http://dx.doi.org/10.1038/nrc3677
24. Armulik A, Genove G, Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 2011;21:193-215; PMID: 21839917; http://dx.doi.org/10.1016/j.devcel.2011.07.001
25. Rzucidlo EM, Martin KA, Powell RJ. Regulation of vascular smooth muscle cell differentiation. J Vasc Surg 2007;45 Suppl A: A25-32; PMID: 17544021; http://dx.doi.org/10.1016/j.jvs.2007.03.001
26. Owens GK, Kumar MS, Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 2004;84:767-801; PMID: 15269336; http://dx.doi.org/10.1152/physrev. 00041.2003
27. Lacolley P, Regnault V, Nicoletti A, Li Z, Michel JB. The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles. Cardiovasc Res 2012;95:194-204; PMID: 22467316; http://dx.doi.org/10.1093/cvr/cvs135
28. Petrova TV, Karpanen T, Norrmen C, Mellor R, Tamakoshi T, Finegold D, Ferrell R, Kerjaschki D, Mortimer P, Yla-Herttuala S, et al. Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis. Nat Med 2004;10:974-81; PMID: 15322537; http://dx.doi.org/10.1038/nm1094
29. Makinen T, Adams RH, Bailey J, Lu Q, Ziemiecki A, Alitalo K, Klein R, Wilkinson GA. PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature. Genes Dev 2005;19:397-410; PMID: 15687262; http://dx.doi.org/10.1101/gad. 330105
30. Lutter S, Xie S, Tatin F, Makinen T. Smooth muscleendothelial cell communication activates Reelin signaling and regulates lymphatic vessel formation. J Cell Biol 2012;197:837-49; PMID: 22665518; http://dx. doi.org/10.1083/jcb.201110132
31. Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 2004;56:549-80; PMID: 15602010; http://dx.doi.org/10.1124/pr.56.4.3
32. Blanco R, Gerhardt H. VEGF and Notch in tip and stalk cell selection. Cold Spring Harb Perspect Med 2013;3:a006569; PMID: 23085847; http://dx.doi.org/10.1101/cshperspect.a006569
33. Gerhardt H. VEGF and endothelial guidance in angiogenic sprouting. Organogenesis 2008;4:241-6; PMID: 19337404; http://dx.doi.org/10.4161/org.4.4.7414
34. Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling-in control of vascular function. Nat Rev Mol Cell Biol 2006;7:359-71; PMID: 16633338; http://dx.doi.org/10.1038/nrm1911
35. Hagberg CE, Falkevall A, Wang X, Larsson E, Huusko J, Nilsson I, Van Meeteren LA, Samen E, Lu L, Vanwildemeersch M, et al. Vascular endothelial growth factor B controls endothelial fatty acid uptake. Nature 2010;464:917-21; PMID: 20228789; http://dx.doi.org/10.1038/nature08945
36. Haiko P, Makinen T, Keskitalo S, Taipale J, Karkkainen MJ, Baldwin ME, Stacker SA, Achen MG, Alitalo K. Deletion of vascular endothelial growth factor C (VEGF-C) and VEGF-D is not equivalent to VEGF receptor 3 deletion in mouse embryos. Mol Cell Biol 2008;28:4843-50; PMID: 18519586; http://dx.doi.org/10.1128/MCB.02214-07
37. Yamazaki Y, Morita T. Molecular and functional diversity of vascular endothelial growth factors. Mol Divers 2006;10:515-27; PMID: 16972015; http://dx. doi.org/10.1007/s11030-006-9027-3
38. Koch S, Claesson-Welsh L. Signal transduction by vascular endothelial growth factor receptors. Cold Spring Harb Perspect Med 2012;2:a006502; PMID: 22762016; http://dx.doi.org/10.1101/cshperspect.a006502
39. Harper SJ, Bates DO. VEGF-A splicing: the key to anti-angiogenic therapeutics? Nat Rev Cancer 2008;8:880-7; PMID: 18923433; http://dx.doi.org/10. 1038/nrc2505
40. Lee S, Chen TT, Barber CL, Jordan MC, Murdock J, Desai S, Ferrara N, Nagy A, Roos KP, Iruela-Arispe ML. Autocrine VEGF signaling is required for vascular homeostasis. Cell 2007;130:691-703; PMID: 17719546; http://dx.doi.org/10.1016/j. cell.2007.06.054
41. Kaipainen A, Korhonen J, Mustonen T, Van Hinsbergh VW, Fang GH, Dumont D, Breitman M, Alitalo K. Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci U S A 1995;92:3566-70; PMID: 7724599; http://dx.doi.org/10.1073/pnas.92.8.3566
42. Dumont DJ, Jussila L, Taipale J, Lymboussaki A, Mustonen T, Pajusola K, Breitman M, Alitalo K. Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science 1998;282:946-9; PMID: 9794766; http://dx.doi.org/10.1126/science.282.5390.946
43. Tammela T, Zarkada G, Wallgard E, Murtomaki A, Suchting S, Wirzenius M, Waltari M, Hellstrom M, Schomber T, Peltonen R, et al. Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation. Nature 2008;454:656-60; PMID: 18594512; http://dx.doi.org/10.1038/nature07083
44. Siekmann AF, Lawson ND. Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries. Nature 2007;445:781-4; PMID: 17259972; http://dx.doi.org/10.1038/nature05577
45. Tammela T, Zarkada G, Nurmi H, Jakobsson L, Heinolainen K, Tvorogov D, Zheng W, Franco CA, Murtomaki A, Aranda E, et al. VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling. Nat Cell Biol 2011;13:1202-13; PMID: 21909098; http://dx.doi.org/10.1038/ncb2331
46. Benedito R, Rocha SF, Woeste M, Zamykal M, Radtke F, Casanovas O, Duarte A, Pytowski B, Adams RH. Notch-dependent VEGFR3 upregulation allows angiogenesis without VEGF-VEGFR2 signalling. Nature 2012;484:110-4; PMID: 22426001; http://dx.doi.org/10.1038/nature10908
47. Avraamides CJ, Garmy-Susini B, Varner JA. Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 2008;8:604-17; PMID: 18497750; http://dx.doi.org/10.1038/nrc2353
48. Augustin HG, Koh GY, Thurston G, Alitalo K. Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol 2009;10:165-77; PMID: 19234476; http://dx.doi.org/10.1038/nrm2639
49. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997;277:55-60; PMID: 9204896; http://dx.doi.org/10.1126/science.277.5322.55
50. Koh GY. Orchestral actions of angiopoietin-1 in vascular regeneration. Trends Mol Med 2013;19:31-9; PMID: 23182855; http://dx.doi.org/10.1016/j. molmed.2012.10.010
51. Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 1996;87:1171-80; PMID: 8980224; http://dx.doi.org/10.1016/S0092-8674 (00) 81813-9
52. Gale NW, Thurston G, Hackett SF, Renard R, Wang Q, McClain J, Martin C, Witte C, Witte MH, Jackson D, et al. Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1. Dev Cell 2002;3:411-23; PMID: 12361603; http://dx.doi.org/10.1016/S1534-5807 (02) 00217-4
53. Thomas M, Felcht M, Kruse K, Kretschmer S, Deppermann C, Biesdorf A, Rohr K, Benest AV, Fiedler U, Augustin HG. Angiopoietin-2 stimulation of endothelial cells induces alphavbeta3 integrin internalization and degradation. J Biol Chem 2010;285:23842-9; PMID: 20519501; http://dx.doi.org/10.1074/jbc. M109.097543
54. Heldin CH, Lennartsson J. Structural and functional properties of platelet-derived growth factor and stem cell factor receptors. Cold Spring Harb Perspect Biol 2013;5:a009100; PMID: 23906712; http://dx.doi.org/10.1101/cshperspect.a009100
55. Heldin CH. Targeting the PDGF signaling pathway in tumor treatment. Cell Commun Signal 2013;11:97; PMID: 24359404; http://dx.doi.org/10.1186/1478-811X-11-97
56. Del Toro R, Prahst C, Mathivet T, Siegfried G, Kaminker JS, Larrivee B, Breant C, Duarte A, Takakura N, Fukamizu A, et al. Identification and functional analysis of endothelial tip cell-enriched genes. Blood 2010;116:4025-33; PMID: 20705756; http://dx.doi.org/10.1182/blood-2010-02-270819
57. Tallquist M, Kazlauskas A. PDGF signaling in cells and mice. Cytokine Growth Factor Rev 2004;15:205-13; PMID: 15207812; http://dx.doi.org/10.1016/j.cytogfr.2004.03.003
58. Adams RH, Wilkinson GA, Weiss C, Diella F, Gale NW, Deutsch U, Risau W, Klein R. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev 1999;13:295-306; PMID: 9990854; http://dx. doi.org/10.1101/gad.13.3.295
59. Gerety SS, Wang HU, Chen ZF, Anderson DJ. Symmetrical mutant phenotypes of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development. Mol Cell 1999;4:403-14; PMID: 10518221; http://dx.doi.org/10.1016/S1097-2765 (00) 80342-1
60. Wang HU, Chen ZF, Anderson DJ. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 1998;93:741-53; PMID: 9630219; http://dx.doi.org/10.1016/S0092-8674 (00) 81436-1
61. Adams RH, Diella F, Hennig S, Helmbacher F, Deutsch U, Klein R. The cytoplasmic domain of the ligand ephrinB2 is required for vascular morphogenesis but not cranial neural crest migration. Cell 2001;104:57-69; PMID: 11163240; http://dx.doi.org/10.1016/S0092-8674 (01) 00191-X
62. Foo SS, Turner CJ, Adams S, Compagni A, Aubyn D, Kogata N, Lindblom P, Shani M, Zicha D, Adams RH. Ephrin-B2 controls cell motility and adhesion during blood-vessel-wall assembly. Cell 2006;124:161-73; PMID: 16413489; http://dx.doi.org/10.1016/j.cell.2005.10.034
63. Salvucci O, De La Luz Sierra M, Martina JA, McCormick PJ, Tosato G. EphB2 and EphB4 receptors forward signaling promotes SDF-1-induced endothelial cell chemotaxis and branching remodeling. Blood 2006;108:2914-22; PMID: 16840724; http://dx.doi.org/10.1182/blood-2006-05-023341
64. Wang Y, Nakayama M, Pitulescu ME, Schmidt TS, Bochenek ML, Sakakibara A, Adams S, Davy A, Deutsch U, Luthi U, et al. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature 2010;465:483-6; PMID: 20445537; http://dx.doi.org/10.1038/nature09002
65. Sawamiphak S, Seidel S, Essmann CL, Wilkinson GA, Pitulescu ME, Acker T, Acker-Palmer A. Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis. Nature 2010;465:487-91; PMID: 20445540; http://dx.doi.org/10.1038/nature08995
66. Katsuta H, Fukushima Y, Maruyama K, Hirashima M, Nishida K, Nishikawa S, Uemura A. EphrinB2-EphB4 signals regulate formation and maintenance of funnel-shaped valves in corneal lymphatic capillaries. Invest Ophthalmol Vis Sci 2013;54:4102-8; PMID: 23696610; http://dx.doi.org/10.1167/iovs. 12-11436
67. Pasquale EB. Eph-ephrin bidirectional signaling in physiology and disease. Cell 2008;133:38-52; PMID: 18394988; http://dx.doi.org/10.1016/j.cell. 2008.03.011
68. Batlle E, Wilkinson DG. Molecular mechanisms of cell segregation and boundary formation in development and tumorigenesis. Cold Spring Harb Perspect Biol 2012;4:a008227; PMID: 22214769
69. Pasquale EB. Eph receptor signalling casts a wide net on cell behaviour. Nat Rev Mol Cell Biol 2005;6:462-75; PMID: 15928710; http://dx.doi.org/10.1038/nrm1662
70. Singh A, Winterbottom E, Daar IO. Eph/ephrin signaling in cell-cell and cell-substrate adhesion. Front Biosci (Landmark Ed) 2012;17:473-97; PMID: 22201756; http://dx.doi.org/10.2741/3939
71. Daar IO. Non-SH2/PDZ reverse signaling by ephrins. Semin Cell Dev Biol 2012;23:65-74; PMID: 22040914; http://dx.doi.org/10.1016/j. semcdb. 2011.10.012
72. Lee HS, Daar IO. EphrinB reverse signaling in cellcell adhesion: is it just par for the course? Cell Adh Migr 2009;3:250-5; PMID: 19276658; http://dx.doi.org/10.4161/cam.3.3.8211
73. Marquardt T, Shirasaki R, Ghosh S, Andrews SE, Carter N, Hunter T, Pfaff SL. Coexpressed EphA receptors and ephrin-A ligands mediate opposing actions on growth cone navigation from distinct membrane domains. Cell 2005;121:127-39; PMID: 15820684; http://dx.doi.org/10.1016/j.cell.2005.01.020
74. Xu NJ, Sun S, Gibson JR, Henkemeyer M. A dual shaping mechanism for postsynaptic ephrin-B3 as a receptor that sculpts dendrites and synapses. Nat Neurosci 2011;14:1421-9; PMID: 21964490; http://dx. doi.org/10.1038/nn. 2931
75. Davis S, Gale NW, Aldrich TH, Maisonpierre PC, Lhotak V, Pawson T, Goldfarb M, Yancopoulos GD. Ligands for EPH-related receptor tyrosine kinases that require membrane attachment or clustering for activity. Science 1994;266:816-9; PMID: 7973638; http://dx.doi.org/10.1126/science.7973638
76. Stein E, Lane AA, Cerretti DP, Schoecklmann HO, Schroff AD, Van Etten RL, Daniel TO. Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses. Genes Dev 1998;12:667-78; PMID: 9499402; http://dx.doi.org/10.1101/gad. 12.5.667
77. Seiradake E, Schaupp A, Del Toro Ruiz D, Kaufmann R, Mitakidis N, Harlos K, Aricescu AR, Klein R, Jones EY. Structurally encoded intraclass differences in EphA clusters drive distinct cell responses. Nat Struct Mol Biol 2013;20:958-64; PMID: 23812375; http://dx.doi.org/10.1038/nsmb.2617
78. Klein R, Kania A. Ephrin signalling in the developing nervous system. Curr Opin Neurobiol 2014;27C: 16-24; http://dx.doi.org/10.1016/j.conb.2014.02.006
79. Xu K, Tzvetkova-Robev D, Xu Y, Goldgur Y, Chan YP, Himanen JP, Nikolov DB. Insights into Eph receptor tyrosine kinase activation from crystal structures of the EphA4 ectodomain and its complex with ephrin-A5. Proc Natl Acad Sci U S A 2013;110:14634-9; PMID: 23959867; http://dx.doi.org/10.1073/pnas.1311000110
80. Himanen JP, Rajashankar KR, Lackmann M, Cowan CA, Henkemeyer M, Nikolov DB. Crystal structure of an Eph receptor-ephrin complex. Nature 2001;414:933-8; PMID: 11780069; http://dx.doi.org/10.1038/414933a
81. Huynh-Do U, Stein E, Lane AA, Liu H, Cerretti DP, Daniel TO. Surface densities of ephrin-B1 determine EphB1-coupled activation of cell attachment through alphavbeta3 and alpha5beta1 integrins. EMBO J 1999;18:2165-73; PMID: 10205170; http://dx.doi.org/10.1093/emboj/18.8.2165
82. Himanen JP, Nikolov DB. Eph signaling: a structural view. Trends Neurosci 2003;26:46-51; PMID: 12495863; http://dx.doi.org/10.1016/S0166-2236 (02) 00005-X
83. Himanen JP, Yermekbayeva L, Janes PW, Walker JR, Xu K, Atapattu L, Rajashankar KR, Mensinga A, Lackmann M, Nikolov DB, et al. Architecture of Eph receptor clusters. Proc Natl Acad Sci U S A 2010;107:10860-5; PMID: 20505120; http://dx.doi.org/10.1073/pnas.1004148107
84. Schaupp A, Sabet O, Dudanova I, Ponserre M, Bastiaens P, Klein R. The composition of EphB2 clusters determines the strength in the cellular repulsion response. J Cell Biol 2014;204:409-22; PMID: 24469634; http://dx.doi.org/10.1083/jcb. 201305037
85. Wimmer-Kleikamp SH, Janes PW, Squire A, Bastiaens PI, Lackmann M. Recruitment of Eph receptors into signaling clusters does not require ephrin contact. J Cell Biol 2004;164:661-6; PMID: 14993233; http://dx.doi.org/10.1083/jcb.200312001
86. Singla N, Goldgur Y, Xu K, Paavilainen S, Nikolov DB, Himanen JP. Crystal structure of the ligandbinding domain of the promiscuous EphA4 receptor reveals two distinct conformations. Biochem Biophys Res Commun 2010;399:555-9; PMID: 20678482; http://dx.doi.org/10.1016/j.bbrc.2010.07.109
87. Pasquale EB. Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat Rev Cancer 2010;10:165-80; PMID: 20179713; http://dx.doi.org/10.1038/nrc2806
88. Pitulescu ME, Adams RH. Eph/ephrin molecules-a hub for signaling and endocytosis. Genes Dev 2010;24:2480-92; PMID: 21078817; http://dx.doi.org/10.1101/gad.1973910
89. Li W, Mukouyama YS. Tissue-specific venous expression of the EPH family receptor EphB1 in the skin vasculature. Dev Dyn 2013;242:976-88; PMID: 23649798; http://dx.doi.org/10.1002/dvdy.23985
90. Zhong TP, Childs S, Leu JP, Fishman MC. Gridlock signalling pathway fashions the first embryonic artery. Nature 2001;414:216-20; PMID: 11700560; http://dx.doi.org/10.1038/35102599
91. Visconti RP, Richardson CD, Sato TN. Orchestration of angiogenesis and arteriovenous contribution by angiopoietins and vascular endothelial growth factor (VEGF). Proc Natl Acad Sci U S A 2002;99:8219-24; PMID: 12048246; http://dx.doi.org/10.1073/pnas.122109599
92. Mukouyama YS, Shin D, Britsch S, Taniguchi M, Anderson DJ. Sensory nerves determine the pattern of arterial differentiation and blood vessel branching in the skin. Cell 2002;109:693-705; PMID: 12086669; http://dx.doi.org/10.1016/S0092-8674 (02) 00757-2
93. Lawson ND, Vogel AM, Weinstein BM. sonic hedgehog and vascular endothelial growth factor act upstream of the Notch pathway during arterial endothelial differentiation. Dev Cell 2002;3:127-36; PMID: 12110173; http://dx.doi.org/10.1016/S1534-5807 (02) 00198-3
94. Torres-Vazquez J, Kamei M, Weinstein BM. Molecular distinction between arteries and veins. Cell Tissue Res 2003;314:43-59; PMID: 14505031; http://dx. doi.org/10.1007/s00441-003-0771-8
95. Lamont RE, Childs S. MAPping out arteries and veins. Sci STKE 2006;2006: pe39; PMID: 17018851; http://dx.doi.org/10.1126/stke.3552006pe39
96. Lin FJ, Tsai MJ, Tsai SY. Artery and vein formation: a tug of war between different forces. EMBO Rep 2007;8:920-4; PMID: 17906673; http://dx.doi.org/10.1038/sj.embor.7401076
97. Wythe JD, Dang LT, Devine WP, Boudreau E, Artap ST, He D, Schachterle W, Stainier DY, Oettgen P, Black BL, et al. ETS factors regulate Vegf-dependent arterial specification. Dev Cell 2013;26:45-58; PMID: 23830865; http://dx.doi.org/10.1016/j. devcel.2013.06.007
98. Sacilotto N, Monteiro R, Fritzsche M, Becker PW, Sanchez-Del-Campo L, Liu K, Pinheiro P, Ratnayaka I, Davies B, Goding CR, et al. Analysis of Dll4 regulation reveals a combinatorial role for Sox and Notch in arterial development. Proc Natl Acad Sci U S A 2013;110:11893-8; PMID: 23818617; http://dx. doi.org/10.1073/pnas.1300805110
99. Iso T, Maeno T, Oike Y, Yamazaki M, Doi H, Arai M, Kurabayashi M. Dll4-selective Notch signaling induces ephrinB2 gene expression in endothelial cells. Biochem Biophys Res Commun 2006;341:708-14; PMID: 16430858; http://dx.doi.org/10.1016/j.bbrc. 2006.01.020
100. You LR, Lin FJ, Lee CT, De Mayo FJ, Tsai MJ, Tsai SY. Suppression of Notch signalling by the COUPTFII transcription factor regulates vein identity. Nature 2005;435:98-104; PMID: 15875024; http://dx.doi.org/10.1038/nature03511
101. Kim YH, Hu H, Guevara-Gallardo S, Lam MT, Fong SY, Wang RA. Artery and vein size is balanced by Notch and ephrin B2/EphB4 during angiogenesis. Development 2008;135:3755-64; PMID: 18952909; http://dx.doi.org/10.1242/dev. 022475
102. Kohli V, Schumacher JA, Desai SP, Rehn K, Sumanas S. Arterial and venous progenitors of the major axial vessels originate at distinct locations. Dev Cell 2013;25:196-206; PMID: 23639444; http://dx.doi.org/10.1016/j.devcel.2013.03.017
103. Williams C, Kim SH, Ni TT, Mitchell L, Ro H, Penn JS, Baldwin SH, Solnica-Krezel L, Zhong TP. Hedgehog signaling induces arterial endothelial cell formation by repressing venous cell fate. Dev Biol 2010;341:196-204; PMID: 20193674; http://dx.doi.org/10.1016/j.ydbio.2010.02.028
104. Sabin FR. Origin and development of the primitive vessels of the chick and of the pig. Washington: Carnegie Institution of Washington, 1917
105. Carlson TR, Yan Y, Wu X, Lam MT, Tang GL, Beverly LJ, Messina LM, Capobianco AJ, Werb Z, Wang R. Endothelial expression of constitutively active Notch4 elicits reversible arteriovenous malformations in adult mice. Proc Natl Acad Sci U S A 2005;102:9884-9; PMID: 15994223; http://dx.doi.org/10.1073/pnas.0504391102
106. Benedito R, Trindade A, Hirashima M, Henrique D, Da Costa LL, Rossant J, Gill PS, Duarte A. Loss of Notch signalling induced by Dll4 causes arterial calibre reduction by increasing endothelial cell response to angiogenic stimuli. BMC Dev Biol 2008;8:117; PMID: 19087347; http://dx.doi.org/10.1186/1471-213X-8-117
107. Bazigou E, Lyons OT, Smith A, Venn GE, Cope C, Brown NA, Makinen T. Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice. J Clin Invest 2011;121:2984-92; PMID: 21765212; http://dx.doi.org/10.1172/JCI58050
108. Nakayama A, Nakayama M, Turner CJ, Hoing S, Lepore JJ, Adams RH. Ephrin-B2 controls PDGFRbeta internalization and signaling. Genes Dev 2013;27:2576-89; PMID: 24298057; http://dx.doi.org/10.1101/gad.224089.113
109. Nakayama M, Nakayama A, Van Lessen M, Yamamoto H, Hoffmann S, Drexler HC, Itoh N, Hirose T, Breier G, Vestweber D, et al. Spatial regulation of VEGF receptor endocytosis in angiogenesis. Nat Cell Biol 2013;15:249-60; PMID: 23354168; http://dx. doi.org/10.1038/ncb2679
110. Taylor AC, Mendel TA, Mason KE, Degen KE, Yates PA, Peirce SM. Attenuation of ephrinB2 reverse signaling decreases vascularized area and preretinal vascular tuft formation in the murine model of oxygeninduced retinopathy. Invest Ophthalmol Vis Sci 2012;53:5462-70; PMID: 22789927; http://dx.doi.org/10.1167/iovs.11-8599
111. Bochenek ML, Dickinson S, Astin JW, Adams RH, Nobes CD. Ephrin-B2 regulates endothelial cell morphology and motility independently of Eph-receptor binding. J Cell Sci 2010;123:1235-46; PMID: 20233847; http://dx.doi.org/10.1242/jcs.061903
112. Suchting S, Freitas C, Le Noble F, Benedito R, Breant C, Duarte A, Eichmann A. The Notch ligand Deltalike 4 negatively regulates endothelial tip cell formation and vessel branching. Proc Natl Acad Sci U S A 2007;104:3225-30; PMID: 17296941; http://dx.doi.org/10.1073/pnas.0611177104
113. Benedito R, Roca C, Sorensen I, Adams S, Gossler A, Fruttiger M, Adams RH. The Notch Ligands Dll4 and Jagged1 Have Opposing Effects on Angiogenesis. Cell 2009;137:1124-35; PMID: 19524514; http://dx. doi.org/10.1016/j.cell.2009.03.025
114. Siekmann AF, Covassin L, Lawson ND. Modulation of VEGF signalling output by the Notch pathway. Bioessays 2008;30:303-13; PMID: 18348190; http://dx.doi.org/10.1002/bies.20736
115. Horowitz A, Seerapu HR. Regulation of VEGF signaling by membrane traffic. Cellular Signalling 2012;24:1810-20; PMID: 22617029; http://dx.doi.org/10.1016/j.cellsig.2012.05.007
116. Nakayama M, Berger P. Coordination of VEGF receptor trafficking and signaling by coreceptors. Exp Cell Res 2013;319:1340-7; PMID: 23499743; http://dx.doi.org/10.1016/j.yexcr.2013.03.008
117. Lampugnani MG, Orsenigo F, Gagliani MC, Tacchetti C, Dejana E. Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments. J Cell Biol 2006;174:593-604; PMID: 16893970; http://dx.doi.org/10.1083/jcb.200602080
118. Simons M. An inside view: VEGF receptor trafficking and signaling. Physiology (Bethesda) 2012;27:213-22; PMID: 22875452; http://dx.doi.org/10.1152/physiol.00016.2012
119. Labrecque L, Royal I, Surprenant DS, Patterson C, Gingras D, Beliveau R. Regulation of vascular endothelial growth factor receptor-2 activity by caveolin-1 and plasma membrane cholesterol. Mol Biol Cell 2003;14:334-47; PMID: 12529448; http://dx.doi.org/10.1091/mbc. E02-07-0379
120. Carmeliet P, Lampugnani MG, Moons L, Breviario F, Compernolle V, Bono F, Balconi G, Spagnuolo R, Oosthuyse B, Dewerchin M, et al. Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell 1999;98:147-57; PMID: 10428027; http://dx.doi.org/10.1016/S0092-8674 (00) 81010-7
121. Grazia Lampugnani M, Zanetti A, Corada M, Takahashi T, Balconi G, Breviario F, Orsenigo F, Cattelino A, Kemler R, Daniel TO, et al. Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, beta-catenin, and the phosphatase DEP-1/CD148. J Cell Biol 2003;161:793-804; PMID: 12771128; http://dx.doi.org/10.1083/jcb. 200209019
122. Mattila E, Auvinen K, Salmi M, Ivaska J. The protein tyrosine phosphatase TCPTP controls VEGFR2 signalling. J Cell Sci 2008;121:3570-80; PMID: 18840653; http://dx. doi.org/10.1242/jcs.031898
123. Hayashi M, Majumdar A, Li X, Adler J, Sun Z, Vertuani S, Hellberg C, Mellberg S, Koch S, Dimberg A, et al. VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation. Nature Communications 2013;4:1672; PMID: 23575676
124. Zhang X, Lanahan AA, Simons M. VEGFR2 trafficking Speed doesn't kill. Cell Cycle 2013;12:2163-4; PMID: 23803732; http://dx.doi.org/10.4161/cc. 25536
125. Lanahan AA, Hermans K, Claes F, Kerley-Hamilton JS, Zhuang ZW, Giordano FJ, Carmeliet P, Simons M. VEGF receptor 2 endocytic trafficking regulates arterial morphogenesis. Dev Cell 2010;18:713-24; PMID: 20434959; http://dx.doi.org/10.1016/j.devcel. 2010.02.016
126. Pasula S, Cai X, Dong Y, Messa M, McManus J, Chang B, Liu X, Zhu H, Mansat RS, Yoon SJ, et al. Endothelial epsin deficiency decreases tumor growth by enhancing VEGF signaling. J Clin Invest 2012;122:4424-38; PMID: 23187125; http://dx.doi.org/10.1172/JCI64537
127. Andrae J, Gallini R, Betsholtz C. Role of plateletderived growth factors in physiology and medicine. Genes Dev 2008;22:1276-312; PMID: 18483217; http://dx.doi.org/10.1101/gad.1653708
128. Sorkin A, Westermark B, Heldin CH, Claesson-Welsh L. Effect of receptor kinase inactivation on the rate of internalization and degradation of PDGF and the PDGF beta-receptor. J Cell Biol 1991;112:469-78; PMID: 1846866; http://dx.doi.org/10.1083/jcb.112.3.469
129. Sadowski L, Jastrzebski K, Kalaidzidis Y, Heldin CH, Hellberg C, Miaczynska M. Dynamin inhibitors impair endocytosis and mitogenic signaling of PDGF. Traffic 2013;14:725-36; PMID: 23425318; http://dx. doi.org/10.1111/tra.12061
130. Fujita Y, Maruyama S, Kogo H, Matsuo S, Fujimoto T. Caveolin-1 in mesangial cells suppresses MAP kinase activation and cell proliferation induced by bFGF and PDGF. Kidney Int 2004;66:1794-804; PMID: 15496150; http://dx.doi.org/10.1111/j.1523-1755.2004.00954.x
131. Yamamoto H, Sakane H, Yamamoto H, Michiue T, Kikuchi A. Wnt3a and Dkk1 regulate distinct internalization pathways of LRP6 to tune the activation of beta-catenin signaling. Dev Cell 2008;15:37-48; PMID: 18606139; http://dx.doi.org/10.1016/j.devcel.2008.04.015
132. Wang Y, Pennock SD, Chen X, Kazlauskas A, Wang Z. Platelet-derived growth factor receptor-mediated signal transduction from endosomes. J Biol Chem 2004;279:8038-46; PMID: 14660565; http://dx.doi.org/10.1074/jbc. M311494200
133. Boucher P, Gotthardt M, Li WP, Anderson RG, Herz J. LRP: role in vascular wall integrity and protection from atherosclerosis. Science 2003;300:329-32; PMID: 12690199; http://dx.doi.org/10.1126/science. 1082095
134. Zhou L, Takayama Y, Boucher P, Tallquist MD, Herz J. LRP1 regulates architecture of the vascular wall by controlling PDGFRbeta-dependent phosphatidylinositol 3-kinase activation. Plos One 2009;4:e6922; PMID: 19742316; http://dx.doi.org/10.1371/journal. pone.0006922
135. Lehti K, Rose NF, Valavaara S, Weiss SJ, Keski-Oja J. MT1-MMP promotes vascular smooth muscle dedifferentiation through LRP1 processing. J Cell Sci 2009;122:126-35; PMID: 19066283; http://dx.doi.org/10.1242/jcs.035279
136. Muratoglu SC, Mikhailenko I, Newton C, Migliorini M, Strickland DK. Low density lipoprotein receptorrelated protein 1 (LRP1) forms a signaling complex with platelet-derived growth factor receptor-beta in endosomes and regulates activation of the MAPK pathway. J Biol Chem 2010;285:14308-17; PMID: 20220145; http://dx.doi.org/10.1074/jbc. M109.046672
137. Keramati AR, Singh R, Lin A, Faramarzi S, Ye ZJ, Mane S, Tellides G, Lifton RP, Mani A. Wild-type LRP6 inhibits, whereas atherosclerosis-linked LRP6R611C increases PDGF-dependent vascular smooth muscle cell proliferation. Proc Natl Acad Sci U S A 2011;108:1914-8; PMID: 21245321; http://dx.doi.org/10.1073/pnas.1019443108
138. Pellet-Many C, Frankel P, Evans IM, Herzog B, Junemann-Ramirez M, Zachary IC. Neuropilin-1 mediates PDGF stimulation of vascular smooth muscle cell migration and signalling via p130Cas. Biochem J 2011;435:609-18; PMID: 21306301; http://dx.doi.org/10.1042/BJ20100580
139. Kida Y, Duffield JS. Pivotal role of pericytes in kidney fibrosis. Clin Exp Pharmacol Physiol 2011;38:467-73; PMID: 21517936; http://dx.doi.org/10.1111/j.1440-1681.2011.05531.x
140. Kida Y, Ieronimakis N, Schrimpf C, Reyes M, Duffield JS. EphrinB2 reverse signaling protects against capillary rarefaction and fibrosis after kidney injury. J Am Soc Nephrol 2013;24:559-72; PMID: 23492730; http://dx.doi.org/10.1681/ASN.2012080871
141. Lin SL, Chang FC, Schrimpf C, Chen YT, Wu CF, Wu VC, Chiang WC, Kuhnert F, Kuo CJ, Chen YM, et al. Targeting endothelium-pericyte cross talk by inhibiting VEGF receptor signaling attenuates kidney microvascular rarefaction and fibrosis. Am J Pathol 2011;178:911-23; PMID: 21281822; http://dx.doi.org/10.1016/j.ajpath.2010.10.012
142. Pan SY, Chang YT, Lin SL. Microvascular pericytes in healthy and diseased kidneys. Int J Nephrol Renovasc Dis 2014;7:39-48; PMID: 24465134
143. Campanholle G, Ligresti G, Gharib SA, Duffield JS. Cellular mechanisms of tissue fibrosis. 3. Novel mechanisms of kidney fibrosis. Am J Physiol Cell Physiol 2013;304:C591-603; PMID: 23325411; http://dx. doi.org/10.1152/ajpcell.00414.2012
144. Bethani I, Skanland SS, Dikic I, Acker-Palmer A. Spatial organization of transmembrane receptor signalling. EMBO J 2010;29:2677-88; PMID: 20717138; http://dx.doi.org/10.1038/emboj.2010.175
145. Essmann CL, Martinez E, Geiger JC, Zimmer M, Traut MH, Stein V, Klein R, Acker-Palmer A. Serine phosphorylation of ephrinB2 regulates trafficking of synaptic AMPA receptors. Nat Neurosci 2008;11:1035-43; PMID: 19160501; http://dx.doi.org/10.1038/nn. 2171
146. Henkemeyer M, Itkis OS, Ngo M, Hickmott PW, Ethell IM. Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus. J Cell Biol 2003;163:1313-26; PMID: 14691139; http://dx.doi.org/10.1083/jcb.200306033
147. Irie F, Okuno M, Pasquale EB, Yamaguchi Y. EphrinBEphB signalling regulates clathrin-mediated endocytosis through tyrosine phosphorylation of synaptojanin 1. Nat Cell Biol 2005;7:501-9; PMID: 15821731; http://dx.doi.org/10.1038/ncb1252
148. Marler KJ, Becker-Barroso E, Martinez A, Llovera M, Wentzel C, Poopalasundaram S, Hindges R, Soriano E, Comella J, Drescher U. A TrkB/EphrinA interaction controls retinal axon branching and synaptogenesis. J Neurosci 2008;28:12700-12; PMID: 19036963; http://dx.doi.org/10.1523/JNEUROSCI.1915-08.2008
149. Huai J, Drescher U. An ephrin-A-dependent signaling pathway controls integrin function and is linked to the tyrosine phosphorylation of a 120-kDa protein. J Biol Chem 2001;276:6689-94; PMID: 11053419; http://dx.doi.org/10.1074/jbc. M008127200
150. Noren NK, Yang NY, Silldorff M, Mutyala R, Pasquale EB. Ephrin-independent regulation of cell substrate adhesion by the EphB4 receptor. Biochem J 2009;422:433-42; PMID: 19552627; http://dx.doi.org/10.1042/BJ20090014
151. Yamazaki T, Masuda J, Omori T, Usui R, Akiyama H, Maru Y. EphA1 interacts with integrin-linked kinase and regulates cell morphology and motility. J Cell Sci 2009;122:243-55; PMID: 19118217; http://dx.doi.org/10.1242/jcs.036467