TOPOGRAPHY AND RECOGNITION IMAGING OF CELLS - Life at the Nanoscale: Atomic Force Microscopy of Live Cells - page 148

junctions 25 known to be primarily responsible for mechanical linkage
between cells), in which VE-cadherins are clustered and linked through
their cytoplasmic domain to the actin-based cytoskeleton, 26,27 but also plays
an essential role in the remodelling, gating and maturation of vascular
vessels. 28,29 VE-cadherin belongs to the classical type II cadherin subgroup
and shares the common structure with other classical cadherins. It consists
of extracellular ectodomain (EC) containing ive similar repeated subdomains
(EC1-EC5), a single-pass transmembrane domain and a highly conserved
cytoplasmic segment, through which cadherins are connected inside the cell
to a cluster of catenins and thus linked to the actin microilaments ( Fig. 7.3a ) .
This cytoskeletal anchorage is thought to be important for strengthening the
cadherin-mediated adhesion. 27 Homophilic cell-cell adhesion is mediated by
the cadherin extracellular domains, 30 which enable association in parallel
lateral -dimers in physiological Ca 2+ concentration (~1.8 mM) 31-36 as

schematically represented in Fig. 7.3b . The parallel

cis

-dimer is thought to
be the basic structural functional unit for promoting the homophilic bond
between cells, 31,33,36,37 and these

cis

cadherin dimers are assumed to contain one
or two binding sites 31,33,34,38 to form trans -interacting antiparallel tetramers or

adhesion dimers 34 ( Fig. 7.3c ) .

(a) (b) (c)

Figure 7.3. (a) Schematic of VE-cadherin domain organization. As with other
cadherins, VE-cadherin is characterized by the presence of ive sequence repeats
of ~110 amino acids, which form folded Greek-key topology extracellular (EC)
domains. The connections between successive domains are rigidiied by conserved
Ca 2+ -binding sites representing the most signiicant feature of the repeat sequences.
The cytoplasmic domain of VE-cadherin includes the “juxtamembrane region” that
binds p120-catenin (p120 ctn ) and the “catenin binding domain” that interacts with
β -catenin and plakoglobin. (b) In the presence of extracellular calcium (1.8 mM),
the rigid cadherin extracellular domains (shown as grey rods) enable association in
functional

-dimers. The calcium-binding sites between extracellular domains are
shown as yellow stars. (c) These active cadherin cis -dimers promote a homophilic
bond between adjacent cells by forming a trans -adhesion dimer.

cis