Skip to main content

Advertisement

SpringerLink
Log in

VE-cadherin at a glance

  • At-a-glance
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Although being a monolayer the vascular endothelium controls fundamental vessel functions such as permeability, leukocyte extravasation and angiogenesis. The endothelial selective transmembrane constituent of adherens junctions, Vascular Endothelial- (VE-) cadherin plays a crucial role in the regulation of such activities. The signaling pathways controlled by VE-cadherin as well as the ones that regulate VE-cadherin activity start to be elucidated. This delineates a complex network of molecular and functional interactions that can be altered in pathologies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Adam AP, Sharenko AL, Pumiglia K, Vincent PA (2010) Src-induced tyrosine phosphorylation of VE-cadherin is not sufficient to decrease barrier function of endothelial monolayers. J Biol Chem 285:7045–7055

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Baluk P et al (2007) Functionally specialized junctions between endothelial cells of lymphatic vessels. J Exp Med 204:2349–2362

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Baluk P, Hashizume H, McDonald DM (2005) Cellular abnormalities of blood vessels as targets in cancer. Curr Opin Genet Dev 15:102–111

    Article  PubMed  CAS  Google Scholar 

  • Baumeister U et al (2005) Association of Csk to VE-cadherin and inhibition of cell proliferation. Embo J 24:1686–1695

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Boulday G et al (2011) Developmental timing of CCM2 loss influences cerebral cavernous malformations in mice. J Exp Med 208:1835–1847

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Breier G et al (1996) Molecular cloning and expression of murine vascular endothelial-cadherin in early stage development of cardiovascular system. Blood 87:630–641

    PubMed  CAS  Google Scholar 

  • Carmeliet P, Jain RK (2011) Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov 10:417–427

    Article  PubMed  CAS  Google Scholar 

  • Carmeliet P et al (1999) Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell 98:147–157

    Article  PubMed  CAS  Google Scholar 

  • Clevers H, Nusse R (2012) Wnt/beta-catenin signaling and disease. Cell 149:1192–1205

    Article  PubMed  CAS  Google Scholar 

  • Collisson EA, Carranza DC, Chen IY, Kolodney MS (2002) Isoprenylation is necessary for the full invasive potential of RhoA overexpression in human melanoma cells. J Invest Dermatol 119:1172–1176

    Article  PubMed  CAS  Google Scholar 

  • Davis ME et al (2010) Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464:1067–1070

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Dejana E, Tournier-Lasserve E, Weinstein BM (2009) The control of vascular integrity by endothelial cell junctions: molecular basis and pathological implications. Dev Cell 16:209–221

    Article  PubMed  CAS  Google Scholar 

  • Fukuhara S et al (2008) Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1. Nat Cell Biol 10:513–526

    Article  PubMed  CAS  Google Scholar 

  • Gavard J, Gutkind JS (2006) VEGF controls endothelial-cell permeability by promoting the beta-arrestin-dependent endocytosis of VE-cadherin. Nat Cell Biol 8:1223–1234

    Article  PubMed  CAS  Google Scholar 

  • Gavard J, Patel V, GutkindJS (2008) Angiopoietin-1 prevents VEGF-induced endothelial permeability by sequestering Src through mDia. Dev Cell 14:25–36

  • Giampietro C et al (2012) Overlapping and divergent signaling pathways of N-cadherin and VE-cadherin in endothelial cells. Blood 119:2159–2170

    Article  PubMed  CAS  Google Scholar 

  • Glading A, Han J, Stockton RA, Ginsberg MH (2007) KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions. J Cell Biol 179:247–254

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hayashi M et al (2013) VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation. Nat Commun 4:1672

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Iden S et al (2006) A distinct PAR complex associates physically with VE-cadherin in vertebrate endothelial cells. EMBO Rep 7:1239–1246

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kam Y, Quaranta V (2009) Cadherin-bound beta-catenin feeds into the Wnt pathway upon adherens junctions dissociation: evidence for an intersection between beta-catenin pools. PLoS ONE 4:e4580

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kooistra MR, Corada M, Dejana E, Bos JL (2005) Epac1 regulates integrity of endothelial cell junctions through VE-cadherin. FEBS Lett 579:4966–4972

    Article  PubMed  CAS  Google Scholar 

  • Korswagen HC, Herman MA, Clevers HC (2000) Distinct beta-catenins mediate adhesion and signalling functions in C. elegans. Nature 406:527–532

    Article  PubMed  CAS  Google Scholar 

  • Kronstein R et al (2012) Caveolin-1 opens endothelial cell junctions by targeting catenins. Cardiovasc Res 93:130–140

    Article  PubMed  CAS  Google Scholar 

  • Lampugnani MG (2012) Endothelial cell-to-cell junctions: adhesion and signaling in physiology and pathology. Cold Spring Harb Perspect Med 2

  • Lampugnani MG et al (1997) Cell confluence regulates tyrosine phosphorylation of adherens junction components in endothelial cells. J Cell Sci 110(Pt 17):2065–2077

    PubMed  CAS  Google Scholar 

  • Lampugnani MG et al (1995) The molecular organization of endothelial cell to cell junctions: differential association of plakoglobin, beta-catenin, and alpha-catenin with vascular endothelial cadherin (VE-cadherin). J Cell Biol 129:203–217

    Article  PubMed  CAS  Google Scholar 

  • Lampugnani MG, Orsenigo F, Gagliani MC, Tacchetti C, Dejana E (2006) Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments. J Cell Biol 174:593–604

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lampugnani MG et al (2010) CCM1 regulates vascular-lumen organization by inducing endothelial polarity. J Cell Sci 123:1073–1080

    Article  PubMed  CAS  Google Scholar 

  • Lampugnani MG et al (1992) A novel endothelial-specific membrane protein is a marker of cell-cell contacts. J Cell Biol 118:1511–1522

    Article  PubMed  CAS  Google Scholar 

  • Lampugnani MG et al (2002) VE-cadherin regulates endothelial actin activating Rac and increasing membrane association of Tiam. Mol Biol Cell 13:1175–1189

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Maddaluno L et al (2013) EndMT contributes to the onset and progression of cerebral cavernous malformations. Nature 498:492–496

    Article  PubMed  CAS  Google Scholar 

  • Maher MT, Flozak AS, Stocker AM, Chenn A, Gottardi CJ (2009) Activity of the beta-catenin phosphodestruction complex at cell-cell contacts is enhanced by cadherin-based adhesion. J Cell Biol 186:219–228

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • May C et al (2005) Identification of a transiently exposed VE-cadherin epitope that allows for specific targeting of an antibody to the tumor neovasculature. Blood 105:4337–4344

    Article  PubMed  CAS  Google Scholar 

  • Mazzone M et al (2009) Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization. Cell 136:839–851

    Article  PubMed  CAS  Google Scholar 

  • Miyoshi J, Takai Y (2007) Nectin and nectin-like molecules: biology and pathology. Am J Nephrol 27:590–604

    Article  PubMed  CAS  Google Scholar 

  • Nanes BA et al (2012) p120-catenin binding masks an endocytic signal conserved in classical cadherins. J Cell Biol 199:365–380

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Navarro P et al (1995) Catenin-dependent and -independent functions of vascular endothelial cadherin. J Biol Chem 270:30965–30972

    Article  PubMed  CAS  Google Scholar 

  • Nawroth R et al (2002) VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts. Embo J 21:4885–4895

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Nelson WJ (2008) Regulation of cell-cell adhesion by the cadherin-catenin complex. Biochem Soc Trans 36:149–155

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Nitta T et al (2003) Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol 161:653–660

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Oas RG et al (2010) p120-Catenin is required for mouse vascular development. Circ Res 106:941–951

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Orsenigo F et al (2012) Phosphorylation of VE-cadherin is modulated by haemodynamic forces and contributes to the regulation of vascular permeability in vivo. Nat Commun 3:1208

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Pannekoek WJ et al (2011) Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial junction control. Cell Signal 23:2056–2064

    Article  PubMed  CAS  Google Scholar 

  • Park HJ et al (2002) 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors interfere with angiogenesis by inhibiting the geranylgeranylation of RhoA. Circ Res 91:143–150

    Article  PubMed  CAS  Google Scholar 

  • Pokutta S, Drees F, Yamada S, Nelson WJ, Weis WI (2008) Biochemical and structural analysis of alpha-catenin in cell-cell contacts. Biochem Soc Trans 36:141–147

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Potter MD, Barbero S, Cheresh DA (2005) Tyrosine phosphorylation of VE-cadherin prevents binding of p120- and beta-catenin and maintains the cellular mesenchymal state. J Biol Chem 280:31906–31912

    Article  PubMed  CAS  Google Scholar 

  • Rampersad SN et al (2010) Cyclic AMP phosphodiesterase 4D (PDE4D) Tethers EPAC1 in a vascular endothelial cadherin (VE-Cad)-based signaling complex and controls cAMP-mediated vascular permeability. J Biol Chem 285:33614–33622

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Rudini N et al (2008) VE-cadherin is a critical endothelial regulator of TGF-beta signalling. EMBO J 27:993–1004

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Saharinen P et al (2008) Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts. Nat Cell Biol 10:527–537

    Article  PubMed  CAS  Google Scholar 

  • Sakurai A 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

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Sanson B, White P, Vincent JP (1996) Uncoupling cadherin-based adhesion from wingless signalling in Drosophila. Nature 383:627–630

    Article  PubMed  Google Scholar 

  • Simionescu M, Simionescu N, Palade GE (1976) Characteristic endothelial junctions in different segments of the vascular system. Thromb Res 8:247–256

    Article  PubMed  CAS  Google Scholar 

  • Spindler V, Schlegel N, Waschke J (2010) Role of GTPases in control of microvascular permeability. Cardiovasc Res 87:243–253

    Article  PubMed  CAS  Google Scholar 

  • Stahl S et al (2008) Novel CCM1, CCM2, and CCM3 mutations in patients with cerebral cavernous malformations: in-frame deletion in CCM2 prevents formation of a CCM1/CCM2/CCM3 protein complex. Hum Mutat 29:709–717

    Article  PubMed  CAS  Google Scholar 

  • Stockton RA, Shenkar R, Awad IA, Ginsberg MH (2010) Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity. J Exp Med 207:881–896

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Suzuki S, Sano K, Tanihara H (1991) Diversity of the cadherin family: evidence for eight new cadherins in nervous tissue. Cell Regul 2:261–270

    PubMed Central  PubMed  CAS  Google Scholar 

  • Taddei A et al (2008) Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5. Nat Cell Biol 10:923–934

    Article  PubMed  CAS  Google Scholar 

  • Thanou M, Gedroyc W (2013) MRI-Guided Focused Ultrasound as a New Method of Drug Delivery. J Drug Deliv 2013:616197

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Thoreson MA et al (2000) Selective uncoupling of p120(ctn) from E-cadherin disrupts strong adhesion. J Cell Biol 148:189–202

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Turowski P et al (2008) Phosphorylation of vascular endothelial cadherin controls lymphocyte emigration. J Cell Sci 121:29–37

    Article  PubMed  CAS  Google Scholar 

  • Tyler RC, Peterson FC, Volkman BF (2010) Distal interactions within the par3-VE-cadherin complex. Biochemistry 49:951–957

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ukropec JA, Hollinger MK, Salva SM, Woolkalis MJ (2000) SHP2 association with VE-cadherin complexes in human endothelial cells is regulated by thrombin. J Biol Chem 275:5983–5986

    Article  PubMed  CAS  Google Scholar 

  • van Wetering S et al (2002) Reactive oxygen species mediate Rac-induced loss of cell-cell adhesion in primary human endothelial cells. J Cell Sci 115:1837–1846

    PubMed  Google Scholar 

  • Whitehead KJ et al (2009) The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases. Nat Med 15:177–184

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Yamaoka-Tojo M et al (2006) IQGAP1 mediates VE-cadherin-based cell-cell contacts and VEGF signaling at adherence junctions linked to angiogenesis. Arterioscler Thromb Vasc Biol 26:1991–1997

    Article  PubMed  CAS  Google Scholar 

  • Yamashita K et al (2007) Fasudil, a Rho kinase (ROCK) inhibitor, protects against ischemic neuronal damage in vitro and in vivo by acting directly on neurons. Brain Res 1154:215–224

    Article  PubMed  CAS  Google Scholar 

  • Zanetti A et al (2002) Vascular endothelial growth factor induces SHC association with vascular endothelial cadherin: a potential feedback mechanism to control vascular endothelial growth factor receptor-2 signaling. Arterioscler Thromb Vasc Biol 22:617–622

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work is supported by grants from the Fondation Leducq Transatlantic Network of Excellence, Associazione Italiana per la Ricerca sul Cancro (AIRC) and ‘Special ProgramMolecular Clinical Oncology 5X1,000 to AGIMM (AIRC-Gruppo Italiano Malattie Mieloproliferative), the European Community (ENDOSTEM-HEALTH-2009-241440; JUSTBRAIN-HEALTH-2009-241861; ITN Vessels), the European Research Council (ERC) and CARIPLO Foundation.

Author information

Authors and Affiliations

  1. FIRC Institute of Molecular Oncology (IFOM) Fondazione, Via Adamello 16, 20139, Milan, Italy

    Luca Bravi, Elisabetta Dejana & Maria Grazia Lampugnani

  2. Department of Biosciences, School of Sciences, Milan University, Milan, Italy

    Elisabetta Dejana

  3. Mario Negri Institute for Pharmacological Research, Milan, Italy

    Maria Grazia Lampugnani

Authors
  1. Luca Bravi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elisabetta Dejana
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Grazia Lampugnani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Elisabetta Dejana or Maria Grazia Lampugnani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bravi, L., Dejana, E. & Lampugnani, M.G. VE-cadherin at a glance. Cell Tissue Res 355, 515–522 (2014). https://doi.org/10.1007/s00441-014-1843-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-014-1843-7

Keywords

Search

Navigation