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 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 [1], [2]. 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 [1], [6].

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].

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