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PMID: 22391038 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Vinculin associates with endothelial VE-cadherin junctions to control force-dependent remodeling.

The Journal of cell biology ·Vol. 196 ·No. 5 ·2012-03-05 ·Pages 641-52

Huveneers S, Oldenburg J, Spanjaard E, van der Krogt G, Grigoriev I, Akhmanova A, Rehmann H, de Rooij J

Abstract

To remodel endothelial cell-cell adhesion, inflammatory cytokine- and angiogenic growth factor-induced signals impinge on the vascular endothelial cadherin (VE-cadherin) complex, the central component of endothelial adherens junctions. This study demonstrates that junction remodeling takes place at a molecularly and phenotypically distinct subset of VE-cadherin adhesions, defined here as focal adherens junctions (FAJs). FAJs are attached to radial F-actin bundles and marked by the mechanosensory protein Vinculin. We show that endothelial hormones vascular endothelial growth factor, tumor necrosis factor α, and most prominently thrombin induced the transformation of stable junctions into FAJs. The actin cytoskeleton generated pulling forces specifically on FAJs, and inhibition of Rho-Rock-actomyosin contractility prevented the formation of FAJs and junction remodeling. FAJs formed normally in cells expressing a Vinculin binding-deficient mutant of α-catenin, showing that Vinculin recruitment is not required for adherens junction formation. Comparing Vinculin-devoid FAJs to wild-type FAJs revealed that Vinculin protects VE-cadherin junctions from opening during their force-dependent remodeling. These findings implicate Vinculin-dependent cadherin mechanosensing in endothelial processes such as leukocyte extravasation and angiogenesis.

MeSH Terms
Actins/genetics,metabolism Adherens Junctions/drug effects,metabolism Antigens, CD/genetics,metabolism Cadherins/genetics,metabolism Cytoskeletal Proteins/genetics,metabolism Cytoskeleton/metabolism Endothelial Cells/cytology,drug effects,metabolism Endothelium, Vascular/cytology Human Umbilical Vein Endothelial Cells Humans Mechanotransduction, Cellular/physiology Recombinant Fusion Proteins/genetics,metabolism Stress, Mechanical Thrombin/pharmacology Tumor Necrosis Factor-alpha/pharmacology Vascular Endothelial Growth Factor A/pharmacology Vinculin/genetics,metabolism
Chemicals
Actins Antigens, CD Cadherins Cytoskeletal Proteins Recombinant Fusion Proteins Tumor Necrosis Factor-alpha Vascular Endothelial Growth Factor A cadherin 5 Vinculin Thrombin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Huveneers Stephan
Hubrecht Institute for Developmental Biology and Stem Cell Research, University Medical Centre Utrecht, 3584 CT, Utrecht, Netherlands. s.huveneers@hubrecht.eu
Oldenburg Joppe
Spanjaard Emma
van der Krogt Gerard
Grigoriev Ilya
Akhmanova Anna
Rehmann Holger
de Rooij Johan
References (54)
54 references, click to expand
  1. Vinculin nucleates actin polymerization and modifies actin filament structure.
    J Biol Chem. 2009 Oct 30;284(44):30463-73 PMID: 19736312
  2. Structural basis for vinculin activation at sites of cell adhesion.
    Nature. 2004 Jul 29;430(6999):583-6 PMID: 15195105
  3. Substrate stiffening promotes endothelial monolayer disruption through enhanced physical forces.
    Am J Physiol Cell Physiol. 2011 Jan;300(1):C146-54 PMID: 20861463
  4. Adherens junctions connect stress fibres between adjacent endothelial cells.
    BMC Biol. 2010 Feb 02;8:11 PMID: 20122254
  5. Planar polarized actomyosin contractile flows control epithelial junction remodelling.
    Nature. 2010 Dec 23;468(7327):1110-4 PMID: 21068726
  6. Molecular mechanisms and clinical applications of angiogenesis.
    Nature. 2011 May 19;473(7347):298-307 PMID: 21593862
  7. Integrin-dependent actomyosin contraction regulates epithelial cell scattering.
    J Cell Biol. 2005 Oct 10;171(1):153-64 PMID: 16216928
  8. Mechano-coupling and regulation of contractility by the vinculin tail domain.
    Biophys J. 2008 Jan 15;94(2):661-70 PMID: 17890382
  9. Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells.
    J Cell Sci. 1998 Jul;111 ( Pt 13):1853-65 PMID: 9625748
  10. Suppression of vinculin expression by antisense transfection confers changes in cell morphology, motility, and anchorage-dependent growth of 3T3 cells.
    J Cell Biol. 1993 Sep;122(6):1285-94 PMID: 8376463
  11. Cellular abnormalities of blood vessels as targets in cancer.
    Curr Opin Genet Dev. 2005 Feb;15(1):102-11 PMID: 15661540
  12. Cytoskeletal regulation of pulmonary vascular permeability.
    J Appl Physiol (1985). 2001 Oct;91(4):1487-500 PMID: 11568129
  13. Recruitment of the Arp2/3 complex to vinculin: coupling membrane protrusion to matrix adhesion.
    J Cell Biol. 2002 Dec 9;159(5):881-91 PMID: 12473693
  14. The regulation of leucocyte transendothelial migration by endothelial signalling events.
    Cardiovasc Res. 2010 May 1;86(2):202-10 PMID: 20068003
  15. Histamine and thrombin modulate endothelial focal adhesion through centripetal and centrifugal forces.
    J Clin Invest. 1996 Feb 15;97(4):1020-7 PMID: 8613524
  16. Rho signaling and mechanical control of vascular development.
    Curr Opin Hematol. 2008 May;15(3):228-34 PMID: 18391790
  17. Activation of RhoA by thrombin in endothelial hyperpermeability: role of Rho kinase and protein tyrosine kinases.
    Circ Res. 2000 Aug 18;87(4):335-40 PMID: 10948069
  18. TNF-alpha increases tyrosine phosphorylation of vascular endothelial cadherin and opens the paracellular pathway through fyn activation in human lung endothelia.
    Am J Physiol Lung Cell Mol Physiol. 2006 Dec;291(6):L1232-45 PMID: 16891393
  19. The role of adherens junctions and VE-cadherin in the control of vascular permeability.
    J Cell Sci. 2008 Jul 1;121(Pt 13):2115-22 PMID: 18565824
  20. Re-solving the cadherin-catenin-actin conundrum.
    J Biol Chem. 2006 Nov 24;281(47):35593-7 PMID: 17005550
  21. Directed actin polymerization is the driving force for epithelial cell-cell adhesion.
    Cell. 2000 Jan 21;100(2):209-19 PMID: 10660044
  22. Functional domains of alpha-catenin required for the strong state of cadherin-based cell adhesion.
    J Cell Biol. 1999 Mar 22;144(6):1311-22 PMID: 10087272
  23. Roles of Rho/ROCK and MLCK in TNF-alpha-induced changes in endothelial morphology and permeability.
    J Cell Physiol. 2007 Oct;213(1):221-8 PMID: 17476691
  24. VEGF controls endothelial-cell permeability by promoting the beta-arrestin-dependent endocytosis of VE-cadherin.
    Nat Cell Biol. 2006 Nov;8(11):1223-34 PMID: 17060906
  25. Vinculin is a dually regulated actin filament barbed end-capping and side-binding protein.
    J Biol Chem. 2010 Jul 23;285(30):23420-32 PMID: 20484056
  26. alpha-Catenin-vinculin interaction functions to organize the apical junctional complex in epithelial cells.
    J Cell Biol. 1998 Aug 10;142(3):847-57 PMID: 9700171
  27. Mechanosensitive EPLIN-dependent remodeling of adherens junctions regulates epithelial reshaping.
    J Cell Biol. 2011 Aug 22;194(4):643-56 PMID: 21844208
  28. Protein kinase C activation upregulates intercellular adhesion of alpha-catenin-negative human colon cancer cell variants via induction of desmosomes.
    J Cell Biol. 1997 Jun 2;137(5):1103-16 PMID: 9166410
  29. Mechanical tugging force regulates the size of cell-cell junctions.
    Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):9944-9 PMID: 20463286
  30. The mechanical integrin cycle.
    J Cell Sci. 2009 Jan 15;122(Pt 2):179-86 PMID: 19118210
  31. Myosin VI and vinculin cooperate during the morphogenesis of cadherin cell cell contacts in mammalian epithelial cells.
    J Cell Biol. 2007 Jul 30;178(3):529-40 PMID: 17664339
  32. alpha3beta1 integrin-CD151, a component of the cadherin-catenin complex, regulates PTPmu expression and cell-cell adhesion.
    J Cell Biol. 2003 Dec 22;163(6):1351-62 PMID: 14691142
  33. RhoA/ROCK signaling is essential for multiple aspects of VEGF-mediated angiogenesis.
    FASEB J. 2010 Sep;24(9):3186-95 PMID: 20400538
  34. Localized zones of Rho and Rac activities drive initiation and expansion of epithelial cell-cell adhesion.
    J Cell Biol. 2007 Jul 30;178(3):517-27 PMID: 17646397
  35. Strength dependence of cadherin-mediated adhesions.
    Biophys J. 2010 Feb 17;98(4):534-42 PMID: 20159149
  36. KDR stimulates endothelial cell migration through heterotrimeric G protein Gq/11-mediated activation of a small GTPase RhoA.
    J Biol Chem. 2002 Nov 29;277(48):46791-8 PMID: 12244099
  37. Actomyosin tension is required for correct recruitment of adherens junction components and zonula occludens formation.
    Exp Cell Res. 2006 May 15;312(9):1637-50 PMID: 16519885
  38. Vinculin regulates cell-surface E-cadherin expression by binding to beta-catenin.
    J Cell Sci. 2010 Feb 15;123(Pt 4):567-77 PMID: 20086044
  39. Vascular permeability in cardiovascular disease and cancer.
    Curr Opin Hematol. 2008 May;15(3):243-9 PMID: 18391792
  40. Local cortical tension by myosin II guides 3D endothelial cell branching.
    Curr Biol. 2009 Feb 10;19(3):260-5 PMID: 19185493
  41. Thrombin inhibits myosin light chain dephosphorylation in endothelial cells.
    Am J Physiol. 1997 Feb;272(2 Pt 1):L311-9 PMID: 9124383
  42. VE-Cadherin-mediated cell-cell interaction suppresses sprouting via signaling to MLC2 phosphorylation.
    Curr Biol. 2009 Apr 28;19(8):668-74 PMID: 19345098
  43. Alpha-catenin is a molecular switch that binds E-cadherin-beta-catenin and regulates actin-filament assembly.
    Cell. 2005 Dec 2;123(5):903-15 PMID: 16325583
  44. alpha-Catenin as a tension transducer that induces adherens junction development.
    Nat Cell Biol. 2010 Jun;12(6):533-42 PMID: 20453849
  45. Vinculin controls focal adhesion formation by direct interactions with talin and actin.
    J Cell Biol. 2007 Dec 3;179(5):1043-57 PMID: 18056416
  46. Tissue elongation requires oscillating contractions of a basal actomyosin network.
    Nat Cell Biol. 2010 Dec;12(12):1133-42 PMID: 21102441
  47. Cell adhesion dynamics at endothelial junctions: VE-cadherin as a major player.
    Trends Cell Biol. 2009 Jan;19(1):8-15 PMID: 19010680
  48. EPLIN mediates linkage of the cadherin catenin complex to F-actin and stabilizes the circumferential actin belt.
    Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):13-9 PMID: 18093941
  49. Deconstructing the cadherin-catenin-actin complex.
    Cell. 2005 Dec 2;123(5):889-901 PMID: 16325582
  50. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress.
    Nature. 2005 Sep 15;437(7057):426-31 PMID: 16163360
  51. ICAM-1-mediated, Src- and Pyk2-dependent vascular endothelial cadherin tyrosine phosphorylation is required for leukocyte transendothelial migration.
    J Immunol. 2007 Sep 15;179(6):4053-64 PMID: 17785844
  52. Lifeact: a versatile marker to visualize F-actin.
    Nat Methods. 2008 Jul;5(7):605-7 PMID: 18536722
  53. Cell-to-cell adherens junction formation and actin filament organization: similarities and differences between non-polarized fibroblasts and polarized epithelial cells.
    J Cell Sci. 1995 Jan;108 ( Pt 1):127-42 PMID: 7738090
  54. Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner.
    J Cell Biol. 2010 Jun 28;189(7):1107-15 PMID: 20584916
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.201108120
Email
s.huveneers@hubrecht.eu
Published
2012-03-05
Pages
641-52
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC3307691
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.201108120 PMC Full Text View journal details
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