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concentrated pool of α-catenin that favors its dimerization. Thus, α-catenin
dissociates from β-catenin and forms dimers, which in turn associate with
actin filaments. Association of α-catenin to actin filament inhibits the activ-
ity of the Arp2/3 complex and hence, reorganizing F-actin network from
a “branched” to a “bundled” conformation (
Drees et al., 2005
), thereby sta-
bilizing cell-cell adhesions with bundles of cortical actin filaments. In this
context, it is of interest to note that while AJs may connect to the actin
cytoskeleton via the nectin-afadin complex, the strong adhesion provided
by AJs in an epithelium is difficult to achieve without the cadherin-β-
catenin-α-catenin-actin association (
Harris and Tepass, 2010
). Moreover,
when the actin-binding domain of α-catenin is deleted, the directional
movement of cadherin-α-catenin fusion proteins to the apical junctional
complex is abolished, illustrating binding of α-catenin to actin filaments is
essential for actin cytoskeleton-mediated lateral flow of cadherins (
Kam-
etani and Takeichi, 2007
). It seems that there are missing links regarding
how α-catenin connects the cadherin-β-catenin complex to actin cytoskel-
eton, and additional research is needed in this area.
2.2.1.2. Nectins
Nectins are a family of immunoglobulin-like cell adhesion molecules with
four members known to date, namely nectin-1 to -4. In general, each nec-
tin has an extracellular domain which contains three Ig-like loops, a trans-
membrane region and a cytoplasmic tail (
Sakisaka et al., 2007
;
Takai et al.,
2008
). Each nectin member first forms homotypic
cis
-dimers, which in turn
form homotypic or heterotypic
trans
-dimers in a Ca
2+
-independent man-
ner. Interestingly, the adhesive force between heterotypic
trans
-dimers is
stronger than that between homotypic
trans
-dimers (
Sakisaka et al., 2007
;
Takai et al., 2008
). Nectins are connected to actin cytoskeleton via a cyto-
plasmic adaptor afadin (
Sakisaka et al., 2007
;
Takai et al., 2008
). Besides
binding to nectins via PDZ domain and actin filaments via its C-terminal
tail, afadin indeed has multiple domains, enabling it to associate with dif-
ferent proteins, such as c-Src, Rap1 (a small G protein), ZO-1, α-catenin
(
Sakisaka et al., 2007
;
Takai et al., 2008
). This thus mediates signal trans-
duction and provides cross talk between cadherin- and nectin-based junc-
tions. Studies have demonstrated that by coupling with actin reorganization,
nectins are responsible for initiating AJ formation and for recruiting cad-
herins to complete the process. As epithelial cells initiate cell-cell contact,
trans
-interacting nectins from adjacent cells were found to activate Cdc42
(a small GTPase of the Rho-subfamily), Rac (also a signaling GTPase) via
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