Map Key
Generic Enzyme
Generic kinase
Protein kinase
Lipid kinase
Generic phosphatase
Protein phosphatase
Lipid phosphatase
Generic phospholipase
Generic protease
Metalloprotease
G-alpha
RAS - superfamily
G beta/gamma
Regulators (GDI, GAP, GEF)
Generic channel
Ligand-gated channel
Voltage-gated channel
Transporter
Normal process
Pathological process
Positive effect
Negative effect
Unspecified effect
Technical link
Disrupts in disease
Emerges in disease
Enhances in disease
Weakens in disease
Organsim specific interaction

Generic binding protein
Receptor ligand
Cell membrane glycoprotein
Transcription factor
DNA
RNA
Compound
Inorganic ion
Predicted metabolite or user's structure
Reaction
Generic receptor
GPCR
Receptors with enzyme activity
Mitochondria
EPR
Golgi
Nucleus
Lysosome
Peroxisome
Cytoplasm
Extracellular

Normal process
Pathological process
Binding
Cleavage
Covalent modifications
Phosphorylation
Dephosphorylation
Transformation
Transport
Catalysis
Transcription regulation
MicroRNA binding
Competition
Influence on expression
Unspecified interactions
Pharmacological effect
Toxic effect
Group relation
Complex subunit
Similarity reaction
A complex or a group
Organism specific object

Cell adhesion Endothelial cell contacts by junctional mechanisms


Log In to Post A Comment

Cell adhesion Endothelial cell contacts by junctional mechanisms

Endothelial cell contacts by junctional mechanisms

Contacts between endothelial cells are important for blood vessel formation. Formationand maintenance of endothelial cell contacts depends on a complex interplay of plasmamembrane proteins, cytoskeleton components, and signaling molecules. Some of thesemolecules are specifically expressed in the specialized cellular 'junctions', whichinclude tight junction, adherens junction, gap junction and desmosomes [1].

Tight junctions seal the endothelial cell layer. They are particularly prolific inendothelia of the blood-brain barrier and in large arteries, in contrast topost-capillary venules [1]. Molecular composition of tight junctions iscomplex. The only known transmembrane constituents of tight junctions in endothelialcells are Occludin, Claudin 1, Claudin 3, Claudin 5,Claudin 14, Junctional adhesion molecule 1 ( JAM1 ), Junctional adhesionmolecule 2 ( JAM2 ) [1]. Several cytoplasmic proteins have beendefined as tight junction-associated: Zonula occludens-1 ( ZO-1 ), Zonulaoccludens-2 ( ZO-2 ), Cingulin, Myeloid/lymphoid or mixed-lineageleukemia; translocated to, 4 ( AF-6 ) [1], [2],Membrane associated guanylate kinase, WW and PDZ domain containing 1 (MAGI-1(BAIAP1) ). ZO-1 and ZO-2 are found in endothelial cells.ZO-1 and ZO-2 are peripheral membrane scaffolding proteins, specificallyassociated with the tight junctions [1]. Their function is tetherigtransmembrane proteins to the Actin cytoskeletal, also part of tightjunctions.

Adherens junctions link an actin bundles between neighboring cells. Adherens junctionsare ubiquitously expressed in endothelia of all vascular beds. Adherens junctions inendothelial cells are formed by homofilic binding of Cadherin 5, type 2, a vascularepithelium cadherin ( VE-cadherin ) [1]. Cadherins are cell adhesionmolecules anchored by their cytoplasmic tails to a network of intracellular cytoplasmicproteins connected to the actin-based microfilament system. Association with Catenins isnessesary for cadherin-mediated cell adhesion. VE-cadherin interacts via siteswithin the C-terminal half of its cytoplasmic tail with either Catenin delta 1 (p120-catenin ) [3] or Catenin (cadherin-associated protein), beta 1(Beta-catenin) [4], Plakoglobin [5] orPlakophilin 4 [3]. Plakophilin 4 and p120-catenin bindwith the same region on the cytoplasmic tail of VE-cadherin. Overexpression ofPlakophilin 4 can displace p120-catenin from intercellular junctions [4]. Beta-catenin and Plakoglobin bind Catenin (cadherin-associatedprotein), alpha 1, 102kDa ( Alpha-catenin ) [6], which, in turn, bindsto Actinin, alpha ( Alpha-actinin ) [7], [8], ZO-1[9] and ZO-2 [10]. Alpha-actinin tetherstransmembrane proteins to the Actin cytoskeletal. When junctions stabilize afterlong periods of confluency, p120-catenin and Beta-catenin dissociate fromVE-cadherin and Plakoglobin [11], [1].MAGI-1(BAIAP1) is mobilized to cell-cell contacts presumably by associating withBeta-catenin. MAGI-1(BAIAP1) is required for VE-cadherin -dependentRap1 activation [12].

Besides VE-cadherin, Cadherin 2, type 1, N-cadherin (neuronal) (N-cadherin ) is also found in endothelial cells. In contrast to VE-cadherin, N-cadherin is not concentrated at adherents junctions, but is distributed overthe whole cell membrane [13], [1]. N-cadherin alsointeracts with Plakoglobin, p120-catenin and Beta-catenin [13].

Gap junctions contain hydrophilic membrane channels that allow direct communicationbetween neighboring cells via diffusion of ions, metabolites, and small cell signalingmolecules. Gap junctions are clusters of transmembrane chanels formed by connexins madeof six connexin monomers [14]. Gap junction proteins, alpha 4, 5 and 1 (Connexin 37, Connexin 40 and Connexin 43 ) are expressed inendothelial cells [1]. Connexins are probably composed of six identicalconnexin subunit (homomeric) or more than one connexin isotype (heteromeric). Twoidentical connexons form homotypic channels, different connexin isotypes form heterotypicchannels. [14]. The cytoplasmic domain of Connexin 43 bindsZO-1 [14], [15], ZO-2 [15] andBeta-catenin [16]. These contacts allow close association between gapjunctions and cadherin-based adherens junction [14].

Classical desmosomes are not found in endothelial cells, although they express thedesmosomal protein Desmoplakin. Desmoplakin is found in desmosome-likestructures that have been called 'complexus adhaerentes' [5], [17]and Vimentin [18].