Structure of artificial and natural VE-cadherin-based adherens junctions.
In vascular endothelium, adherens junctions between endothelial cells are composed of VE-cadherin (vascular endothelial cadherin), an adhesive receptor that is crucial for the proper assembly of vascular structures and the maintenance of vascular integrity. As a classical cadherin, VE-cadherin links endothelial cells together by homophilic interactions mediated by its extracellular part and associates intracellularly with the actin cytoskeleton via catenins. Although, from structural crystallographic data, a dimeric structure arranged in a trans orientation has emerged as a potential mechanism of cell-cell adhesion, the cadherin organization within adherens junctions remains controversial. Concerning VE-cadherin, its extracellular part possesses the capacity to self-associate in solution as hexamers consisting of three antiparallel cadherin dimers. VE-cadherin-based adherens junctions were reconstituted in vitro by assembly of a VE-cadherin EC (extracellular repeat) 1-EC4 hexamer at the surfaces of liposomes. The artificial adherens junctions revealed by cryoelectron microscopy appear as a two-dimensional self-assembly of hexameric structures. This cadherin organization is reminiscent of that found in native desmosomal junctions. Further structural studies performed on native VE-cadherin junctions would provide a better understanding of the cadherin organization within adherens junctions. Homophilic interactions between cadherins are strengthened intracellularly by connection to the actin cytoskeleton. Recently, we have discovered that annexin 2, an actin-binding protein connects the VE-cadherin-catenin complex to the actin cytoskeleton. This novel link is labile and promotes the endothelial cell switch from a quiescent to an angiogenic state.
Taveau
Jean-Christophe
JC
CBMN UMR-CNRS 5248 IECB, Université Bordeaux 1, Avenue des Facultés, 33405 Talence, France.
Dubois
Mathilde
M
Le Bihan
Olivier
O
Trépout
Sylvain
S
Almagro
Sébastien
S
Hewat
Elizabeth
E
Durmort
Claire
C
Heyraud
Stéphanie
S
Gulino-Debrac
Danielle
D
Lambert
Olivier
O
D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism / Q000648:ultrastructure*; D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000502:physiology*; D002448:Cell Adhesion; D020285:Cryoelectron Microscopy / Q000379:methods; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure*; D006801:Humans; D008567:Membranes, Artificial; D008958:Models, Molecular
D000199:Actins; D015820:Cadherins; D008567:Membranes, Artificial