title: Small Rho GTPase-mediated actin dynamics at endothelial adherens junctions.
abstract: VE-cadherin-based cell-cell junctions form the major restrictive barrier of the endothelium to plasma proteins and blood cells. The function of VE-cadherin and the actin cytoskeleton are intimately linked. Vascular permeability factors and adherent leukocytes signal through small Rho GTPases to tightly regulate actin cytoskeletal rearrangements in order to open and re-assemble endothelial cell-cell junctions in a rapid and controlled manner. The Rho GTPases are activated by guanine nucleotide exchange factors (GEFs), conferring specificity and context-dependent control of cell-cell junctions. Although the molecular mechanisms that couple cadherins to actin filaments are beginning to be elucidated, specific stimulus-dependent regulation of the actin cytoskeleton at VE-cadherin-based junctions remains unexplained. Accumulating evidence has suggested that depending on the vascular permeability factor and on the subcellular localization of GEFs, cell-cell junction dynamics and organization are differentially regulated by one specific Rho GTPase. In this Commentary, we focus on new insights how the junctional actin cytoskeleton is specifically and locally regulated by Rho GTPases and GEFs in the endothelium.
authors.affiliation: a Department of Molecular Cell Biology , Sanquin Research and Landsteiner Laboratory, Academic Medical Center Amsterdam, University of Amsterdam , Amsterdam , the Netherlands.
authors.forename: Jaap D
authors.initials: JD
authors.lastname: van Buul
authors.affiliation: b Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory , Academic Medical Center Amsterdam, University of Amsterdam , Amsterdam , the Netherlands.
authors.forename: Ilse
authors.initials: I
authors.lastname: Timmerman
mesh_terms: D000199:Actins / Q000378:metabolism*; D022005:Adherens Junctions / Q000502:physiology*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D004727:Endothelium / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D015820:Cadherins; D020662:Guanine Nucleotide Exchange Factors; D020559:Monomeric GTP-Binding Proteins
keywords: GEF; GTPase; VE-cadherin; endothelium; junction
references.citation: J Biol Chem. 2008 Feb 22;283(8):5014-22
references.pmid: 18089563
references.citation: Eur J Cell Biol. 2008 Oct;87(10):779-92
references.pmid: 18635287
references.citation: Mol Biol Cell. 2012 Aug;23(15):2831-44
references.pmid: 22696684
references.citation: Sci Rep. 2015 Nov 27;5:17225
references.pmid: 26611125
references.citation: Mol Biol Cell. 2007 May;18(5):1734-43
references.pmid: 17332503
references.citation: FEBS Lett. 2005 Sep 12;579(22):4966-72
references.pmid: 16115630
references.citation: Mol Biol Cell. 2002 Apr;13(4):1175-89
references.pmid: 11950930
references.citation: Gene. 2005 Feb 28;347(1):125-35
references.pmid: 15715966
references.citation: J Biol Chem. 2012 Mar 2;287(10):7556-72
references.pmid: 22194609
references.citation: J Cell Biol. 2004 Mar 15;164(6):899-910
references.pmid: 15024035
references.citation: J Cell Biol. 2000 Sep 4;150(5):1161-76
references.pmid: 10974003
references.citation: J Cell Sci. 2007 Jan 1;120(Pt 1):17-22
references.pmid: 17182900
references.citation: Vascul Pharmacol. 2002 Nov;39(4-5):187-99
references.pmid: 12747959
references.citation: Mol Biol Cell. 2012 Jan;23(2):310-23
references.pmid: 22090347
references.citation: Cell Adhes Commun. 1997 Mar;4(6):399-411
references.pmid: 9177902
references.citation: J Cell Biol. 2015 Jan 5;208(1):23-32
references.pmid: 25559184
references.citation: Nat Rev Mol Cell Biol. 2005 Feb;6(2):167-80
references.pmid: 15688002
references.citation: J Cell Biol. 2003 Jan 6;160(1):11-6
references.pmid: 12507993
references.citation: Biochim Biophys Acta. 2009 Apr;1788(4):790-6
references.pmid: 19159611
references.citation: J Clin Invest. 2012 Jun;122(6):1991-2005
references.pmid: 22585576
references.citation: J Cell Sci. 2001 May;114(Pt 10):1829-38
references.pmid: 11329369
references.citation: Nat Commun. 2015 Mar 10;6:6429
references.pmid: 25752958
references.citation: Mol Biol Cell. 2005 Oct;16(10 ):4531-42
references.pmid: 16030252
references.citation: Nat Commun. 2014 May 07;5:3743
references.pmid: 24806444
references.citation: J Anat. 2002 Jun;200(6):549-60
references.pmid: 12162723
references.citation: J Biol Chem. 2001 Sep 7;276(36):33305-8
references.pmid: 11457821
references.citation: Nat Cell Biol. 2006 Nov;8(11):1223-34
references.pmid: 17060906
references.citation: Trends Cell Biol. 2004 Nov;14(11):589-93
references.pmid: 15519846
references.citation: J Cell Biol. 2012 Jan 9;196(1):115-30
references.pmid: 22232703
references.citation: J Biol Chem. 2002 May 24;277(21):18868-74
references.pmid: 11907041
references.citation: Curr Opin Cell Biol. 2005 Oct;17(5):466-74
references.pmid: 16112561
references.citation: Dev Cell. 2008 Jan;14(1):25-36
references.pmid: 18194650
references.citation: Exp Cell Res. 2007 Sep 10;313(15):3285-97
references.pmid: 17686471
references.citation: Am J Physiol Lung Cell Mol Physiol. 2004 Jan;286(1):L37-48
references.pmid: 12807699
references.citation: Thromb Haemost. 2010 Jan;103(1):40-55
references.pmid: 20062930
references.citation: J Biol Chem. 2003 Apr 11;278(15):13265-70
references.pmid: 12551902
references.citation: Cell Adh Migr. 2014;8(2):100-7
references.pmid: 24714377
references.citation: J Cell Sci. 2007 Jan 1;120(Pt 1):86-100
references.pmid: 17164293
references.citation: Circ Res. 2000 Aug 18;87(4):335-40
references.pmid: 10948069
references.citation: J Biol Chem. 2009 Feb 20;284(8):5381-94
references.pmid: 19095647
references.citation: J Clin Invest. 1996 Feb 15;97(4):1020-7
references.pmid: 8613524
references.citation: Cell Tissue Res. 2014 Mar;355(3):545-55
references.pmid: 24519624
references.citation: Science. 2014 Oct 31;346(6209):1254211
references.pmid: 25359979
references.citation: Circ Res. 2000 Mar 17;86(5):549-57
references.pmid: 10720417
references.citation: Science. 2009 Nov 27;326(5957):1208-12
references.pmid: 19965462
references.citation: J Biol Chem. 2009 Sep 18;284(38):25602-11
references.pmid: 19633358
references.citation: J Cell Biol. 1995 Jul;130(1):67-77
references.pmid: 7790378
references.citation: Nat Commun. 2015 Apr 10;6:6725
references.pmid: 25857352
references.citation: Prog Mol Biol Transl Sci. 2013;116:119-44
references.pmid: 23481193
references.citation: Circ Res. 2012 Dec 7;111(12):1517-27
references.pmid: 22965143
references.citation: Development. 2015 Sep 1;142(17 ):3058-70
references.pmid: 26253403
references.citation: J Cell Biol. 2012 Dec 24;199(7):1103-15
references.pmid: 23253477
references.citation: J Cell Biol. 2007 Jul 30;178(3):517-27
references.pmid: 17646397
references.citation: Am J Pathol. 2011 May;178(5):2424-36
references.pmid: 21457935
references.citation: J Cell Sci. 1999 Jun;112 ( Pt 12):1825-34
references.pmid: 10341202
references.citation: J Biol Chem. 2000 Nov 17;275(46):36116-23
references.pmid: 10948190
references.citation: Am J Physiol Cell Physiol. 2003 Aug;285(2):C343-52
references.pmid: 12700137
references.citation: J Cell Physiol. 2009 Sep;220(3):716-26
references.pmid: 19472214
references.citation: Cold Spring Harb Perspect Biol. 2009 Nov;1(5):a002998
references.pmid: 20066121
references.citation: Nat Commun. 2014 Jul 31;5:4525
references.pmid: 25077739
references.citation: Nat Rev Mol Cell Biol. 2001 Dec;2(12):887-97
references.pmid: 11733768
references.citation: Arterioscler Thromb Vasc Biol. 2014 Nov;34(11):2378-86
references.pmid: 25301843
references.citation: Science. 1998 Jan 23;279(5350):509-14
references.pmid: 9438836
references.citation: Nat Cell Biol. 2008 Sep;10(9):1039-50
references.pmid: 19160484
references.citation: Cell. 2000 Jan 21;100(2):209-19
references.pmid: 10660044
references.citation: Microvasc Res. 2009 May;77(3):304-13
references.pmid: 19323978
references.citation: J Cell Sci. 2013 Jan 15;126(Pt 2):403-13
references.pmid: 23524998
references.citation: Cell Signal. 2005 Feb;17(2):131-9
references.pmid: 15494205
references.citation: J Biol Chem. 1995 Dec 29;270(52):30965-72
references.pmid: 8537353
references.citation: Cell Adh Migr. 2012 Nov-Dec;6(6):482-7
references.pmid: 23076143
references.citation: Nat Cell Biol. 2006 Feb;8(2):113-23
references.pmid: 16429128
references.citation: Curr Biol. 2002 Mar 5;12(5):379-82
references.pmid: 11882288
references.citation: J Cell Biol. 2012 Mar 5;196(5):641-52
references.pmid: 22391038
references.citation: Dev Cell. 2010 Jan 19;18(1):39-51
references.pmid: 20152176
references.citation: Mol Biol Cell. 2010 Feb 15;21(4):584-96
references.pmid: 20032304
references.citation: J Cell Biol. 2013 Sep 16;202(6):901-16
references.pmid: 24019534
references.citation: Nat Cell Biol. 2010 Jun;12(6):533-42
references.pmid: 20453849
references.citation: Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11427-32
references.pmid: 23798437
references.citation: Mol Biol Cell. 2014 Jan;25(2):245-56
references.pmid: 24227887
references.citation: J Cell Sci. 2002 May 1;115(Pt 9):1837-46
references.pmid: 11956315
references.citation: J Cell Biol. 1998 May 4;141(3):755-64
references.pmid: 9566974
references.citation: Mol Biol Cell. 2005 Dec;16(12):5514-27
references.pmid: 16176974
references.citation: Mol Biol Cell. 2005 Jun;16(6):2636-50
references.pmid: 15800060
references.citation: Proc Natl Acad Sci U S A. 1996 May 28;93(11):5466-71
references.pmid: 8643598
references.citation: Mol Cell Biol. 2008 Jan;28(2):794-802
references.pmid: 17984225
references.citation: Oncogene. 1998 Jan 15;16(2):147-52
references.pmid: 9464532
references.citation: Cardiovasc Res. 2010 Jul 15;87(2):243-53
references.pmid: 20299335
references.citation: Mol Cell Biol. 2015 Jul;35(14):2495-502
references.pmid: 25963656
references.citation: Annu Rev Cell Dev Biol. 2005;21:247-69
references.pmid: 16212495
references.citation: Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):2643-52
references.pmid: 21885850
references.citation: J Cell Biol. 1995 Apr;129(1):203-17
references.pmid: 7698986
references.citation: J Cell Sci. 2000 Feb;113 ( Pt 4):729-39
references.pmid: 10652265
references.citation: Nat Cell Biol. 2002 Nov;4(11):901-6
references.pmid: 12402047
references.citation: J Cell Sci. 2015 Sep 15;128(18):3514
references.pmid: 26374854
references.citation: Cell. 2005 Jun 3;121(5):667-70
references.pmid: 15935753
references.citation: Biochim Biophys Acta. 2007 Jun;1771(6):719-26
references.pmid: 17428729