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].