Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 455

to links the cadherin-catenin complex

to the actin cytoskeleton. Vascular endothelial (or Cdh5) and possibly neuronal
(or Cdh2) cadherins thus bind to intracellular partners that contribute to signaling
and dynamics of the actin cytoskeleton. 9

α -catenin via β -or γ -catenin. Catenin- α

10 can also tether cadherin-5
to intermediate filaments via desmoplakin to form the complexus adhaerentes ,a
special type of cell junctions. The desmoplakin-vimentin complex corresponds to
an additional agent of mechanical stability.
Catenins-

Catenin- γ

are able to bind to junctional proteins, such as IQ motif-containing
GTPase-activating protein IQGAP1, platelet-endothelial cell adhesion molecule
PECAM1, casein kinase-2, as well as signaling and transcription factors, such
as Wnt, adenomatous polyposis coli Ub ligase, and T-cell factor [ 854 ]. Scaffold
IQGAP1 not only links to

β

-catenin and E-cadherin, but also to small GTPases
CDC42 and Rac, as well as actin, calmodulin, and microtubule-associated cyto-
plasmic linker integral protein CLIP170. 11 Adhesion molecule PECAM1 that is
concentrated in endothelial clefts interacts with Tyr-phosphorylated

β

-catenin and
phosphatase PTPn11. Molecule PECAM1 may participate in modulating adherens
junction assembly and restoring endothelial barrier integrity after injury. In addition,
PECAM1 binds

β

α V β 3 -integrins and regulates the function of α 4 β 1 -and β 2 -

integrins to possibly mediate transendothelial migration of leukocytes.
α -Catenin that links to β -catenin and actin-polymerizing proteins, such as

α -actinin, vinculin, vasodilator-stimulated phosphoprotein, and formin, as well as

actin microfilaments, promotes actin bundling, thereby stabilizing adherens junction
and cleft. Furthermore, actin polymerization is needed for adherens junction
assembly. Non-muscle myosin heavy chain-2A is an another regulator of adherens
junction formation [ 854 ]. Cadherin-5 can regulate intercellular permeability by
modulating GTP binding to and GTP hydrolysis of small GTPases CDC42, Rac,
and RhoA [ 854 ]. Cadherins can interact with actin-related proteic ARP2-ARP3
complex that associates with Wiskott-Aldrich syndrome protein (WASP), cortactin,
and vinculin. Wiskott-Aldrich syndrome protein is an effector of CDC42 GTPase.
The CDC42-ARP2/3-WASP pathway increases actin polymerization. Cadherin-
5 can also activate GTPase Rac via Rac-specific GEF T-cell lymphoma invasion
and metastasis Tiam1. By activating small GTPases, cadherins can control actin
polymerization at intercellular junctions and modulate paracellular permeability.

9 Vascular endothelial (VE)-cadherin, or cadherin-5, is the single member of the cadherin family
restricted to the endothelium. Neuronal (N) cadherin, or cadherin-2, is also expressed in endothelial
cells. Cadherin-2 mainly has a dispersed distribution on plasma membrane. In the presence of
cadherin-5, cadherin-2 is excluded from cell junctions, except during early stages of cellular
confluency [ 853 ]. In addition, cadherin-2 may also be involved in junctions between endothelial
cells and pericytes.
10 A.k.a. plakoglobin.
11 Calmodulin and E-cadherin compete for binding to IQGAP agent. Calmodulin thus impedes
E-cadherin-mediated homophilic adhesion. Activated CDC42 and Rac1 preclude interaction of
IQGAP1 with

β

-catenin. Activated CDC42 and Rac strengthen endothelial barrier by freeing

β

IQGAP from -catenin.