Pathway Map Details

Cell adhesion_Endothelial cell contacts by non-junctional mechanisms



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MAGI-1(BAIAP1), Alpha-2/beta-1 integrin, Actin cytoskeletal, Laminin 1, Alpha-6/beta-1 integrin, N-cadherin, Alpha-actinin, Collagen IV, Plakoglobin, ESAM, Alpha-3/beta-1 integrin, PECAM1, p120-catenin, Alpha-V/beta-3 integrin, Alpha-5/beta-1 integrin, N-cadherin, Alpha-V/beta-5 integrin, PECAM1, Beta-catenin, Fibronectin, Laminin 8, Collagen I, Alpha-6/beta-4 integrin, Alpha-1/beta-1 integrin, Alpha-catenin, N-cadherin, Vitronectin, ESAM, N-cadherin

Description:

Endothelial cell contacts by non-junctional mechanisms

Contacts between endothelial cells are of great importance for blood vessel formation. The formation and maintenance of endothelial cell contacts require the complex interplay of plasma membrane proteins, cytoskeleton components, and signaling molecules. Some of these molecules are specifically expressed in specialized cellular 'junctions'. There are several types of cellular junctions including: tight junctions, adherens junctions and gap junctions. Some molecules form endothelial cell-cell contacts by non-junctional mechanisms regulated by Cadherin 2, type 1, N-cadherin (neuronal) ( N-cadherin ) , Platelet/endothelial cell adhesion molecule ( PECAM-1 ), Endothelial cell adhesion molecules ( ESAM ) [1].

N-cadherin is found in endothelial cells. N-cadherin is not concentrated at adherens junctions, but is distributed over the whole cell membrane. N-cadherins supports contacts between endothelial cells and smooth muscle cells or pericytes [2], [1]. N-cadherin is a cell adhesion molecule, which is anchored with its cytoplasmic tail to a network of intracellular cytoplasmic proteins that are connected to the actin-based microfilament system. Association with catenins is nessesary for cadherin-mediated cell adhesion. N-cadherin associates via sites within the C-terminal half of its cytoplasmic tail with either Catenin delta 1 ( p120-catenin ) or Catenin (cadherin-associated protein), beta 1 (Beta-catenin) or Junction plakoglobin (Plakoglobin) [2]. Beta-catenin and Plakoglobin bind Catenin (cadherin-associated protein), alpha 1, 102kDa ( Alpha-catenin ) [3], which in turn binds to Actinin, alpha ( Alpha-actinin ) [4], [5].

PECAM-1 is a transmembrane protein in the inter-endothelial cell contacts. PECAM-1 is a homophilic adhesive molecule that is diffusely distributed on subconfluently growing endothelial cells, but concentrates at cell-cell borders upon cell-cell contact PECAM-1 is not restricted to any type of junction. PECAM-1 was shown to co-immunoprecipitate with Beta-catenin in endothelial cells [6], [1].

ESAM is a member of the immunoglobulin superfamily. ESAM is selectively expressed in vascular endothelial cells. ESAM mediates cell-cell adhesion through homophilic interactions [7]. Membrane associated guanylate kinase, WW and PDZ domain containing 1 ( MAGI-1(BAIAP1) ) is a one of the intracellular binding partners of ESAM. ESAM binds directly to the multidomain adaptor MAGI-1(BAIAP1) and recruits it to the cell contacts and the cytoskeleton [8].

Besides inter-endothelial cell-cell contacts, endothelial cell adhesion to the numerous components of the extracellular matrix (ECM) is important in the angiogenesis [9]. Integrins are receptors for different ECM proteins (e.g. Collagen I, Collagen IV, Laminin 1, Laminin 8, Fibronectin and Vitronectin [10], [11], [12], [13]. Interactions between integrins and the ECM proteins result in focal cell adhesion and cytoskeletal remodeling [14], [15].

References:

  1. Vestweber D
    Molecular mechanisms that control endothelial cell contacts. The Journal of pathology 2000 Feb;190(3):281-91
  2. Navarro P, Ruco L, Dejana E
    Differential localization of VE- and N-cadherins in human endothelial cells: VE-cadherin competes with N-cadherin for junctional localization. The Journal of cell biology 1998 Mar 23;140(6):1475-84
  3. Ozawa M
    Identification of the region of alpha-catenin that plays an essential role in cadherin-mediated cell adhesion. The Journal of biological chemistry 1998 Nov 6;273(45):29524-9
  4. Nieset JE, Redfield AR, Jin F, Knudsen KA, Johnson KR, Wheelock MJ
    Characterization of the interactions of alpha-catenin with alpha-actinin and beta-catenin/plakoglobin. Journal of cell science 1997 Apr;110 ( Pt 8):1013-22
  5. Lilien J, Balsamo J
    The regulation of cadherin-mediated adhesion by tyrosine phosphorylation/dephosphorylation of beta-catenin. Current opinion in cell biology 2005 Oct;17(5):459-65
  6. Albelda SM, Muller WA, Buck CA, Newman PJ
    Molecular and cellular properties of PECAM-1 (endoCAM/CD31): a novel vascular cell-cell adhesion molecule. The Journal of cell biology 1991 Sep;114(5):1059-68
  7. Hirata Ki, Ishida T, Penta K, Rezaee M, Yang E, Wohlgemuth J, Quertermous T
    Cloning of an immunoglobulin family adhesion molecule selectively expressed by endothelial cells. The Journal of biological chemistry 2001 May 11;276(19):16223-31
  8. Wegmann F, Ebnet K, Du Pasquier L, Vestweber D, Butz S
    Endothelial adhesion molecule ESAM binds directly to the multidomain adaptor MAGI-1 and recruits it to cell contacts. Experimental cell research 2004 Oct 15;300(1):121-33
  9. Hynes RO
    Integrins: bidirectional, allosteric signaling machines. Cell 2002 Sep 20;110(6):673-87
  10. Kirchhofer D, Languino LR, Ruoslahti E, Pierschbacher MD
    Alpha 2 beta 1 integrins from different cell types show different binding specificities. The Journal of biological chemistry 1990 Jan 15;265(2):615-8
  11. Albelda SM, Daise M, Levine EM, Buck CA
    Identification and characterization of cell-substratum adhesion receptors on cultured human endothelial cells. The Journal of clinical investigation 1989 Jun;83(6):1992-2002
  12. Underwood PA, Bennett FA, Kirkpatrick A, Bean PA, Moss BA
    Evidence for the location of a binding sequence for the alpha 2 beta 1 integrin of endothelial cells, in the beta 1 subunit of laminin. The Biochemical journal 1995 Aug 1;309 ( Pt 3):765-71
  13. Kortesmaa J, Yurchenco P, Tryggvason K
    Recombinant laminin-8 (alpha(4)beta(1)gamma(1)). Production, purification,and interactions with integrins. The Journal of biological chemistry 2000 May 19;275(20):14853-9
  14. Luscinskas FW, Lawler J
    Integrins as dynamic regulators of vascular function. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1994 Sep;8(12):929-38
  15. Wu MH
    Endothelial focal adhesions and barrier function. The Journal of physiology 2005 Dec 1;569(Pt 2):359-66