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Cell adhesion Endothelial cell contacts by non-junctional mechanisms


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Cell adhesion Endothelial cell contacts by non-junctional mechanisms

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 interplayof plasma membrane proteins, cytoskeleton components, and signaling molecules. Some ofthese molecules are specifically expressed in specialized cellular 'junctions'. There areseveral types of cellular junctions including: tight junctions, adherens junctions andgap junctions. Some molecules form endothelial cell-cell contacts by non-junctionalmechanisms regulated by Cadherin 2, type 1, N-cadherin (neuronal) ( N-cadherin ), Platelet/endothelial cell adhesion molecule ( PECAM-1 ), Endothelial celladhesion molecules ( ESAM ) [1].

N-cadherin is found in endothelial cells. N-cadherin is not concentratedat adherens junctions, but is distributed over the whole cell membrane.N-cadherins supports contacts between endothelial cells and smooth muscle cells orpericytes [2], [1]. N-cadherin is a cell adhesionmolecule, which is anchored with its cytoplasmic tail to a network of intracellularcytoplasmic 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 tailwith either Catenin delta 1 ( p120-catenin ) or Catenin (cadherin-associatedprotein), 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 onsubconfluently growing endothelial cells, but concentrates at cell-cell borders uponcell-cell contact PECAM-1 is not restricted to any type of junction.PECAM-1 was shown to co-immunoprecipitate with Beta-catenin in endothelialcells [6], [1].

ESAM is a member of the immunoglobulin superfamily. ESAM is selectivelyexpressed in vascular endothelial cells. ESAM mediates cell-cell adhesion throughhomophilic interactions [7]. Membrane associated guanylate kinase, WW andPDZ domain containing 1 ( MAGI-1(BAIAP1) ) is a one of the intracellular bindingpartners of ESAM. ESAM binds directly to the multidomain adaptorMAGI-1(BAIAP1) and recruits it to the cell contacts and the cytoskeleton [8].

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