Regulation of Blood–Testis Barrier (BTB) Dynamics during Spermatogenesis via the “Yin” and “Yang” Effects of Mammalian Target of Rapamycin Complex 1 (mTORC1) and mTORC2 - International Review of Cell and Molecular Biology - page 308

classical cadherins, such as E-cadherin and N-cadherin ( Radice et al., 1997 ).
In rodent testis, the above two classical cadherins are found at the basal ES
( Mruk et al., 2008 ; Yan et al., 2007 ). They are single span membrane pro-
tein having a divergent extracellular domain containing five repeats called
ectodomain modules (ECs) and a conserved cytoplasmic tail ( Harris and
Tepass, 2010 ; Yonemura, 2011 ). Binding of Ca 2+ ions is necessary for cor-
rect protein confirmation of the ECs, which participate in forming homo-
typic cis -dimers of cadherins on the same side of two neighboring cells.
Two cis -dimers of cadherins from each adjacent cells then form homotypic
trans oligomers that create an AJ ( Harris and Tepass, 2010 ; Yonemura, 2011 ).
Although the binding between cadherin extracellular domains is weak,
cell-cell adhesion is strengthened via lateral clustering of cadherins, which
is a process mediated by nectins ( Sakisaka et al., 2007 ; Takai et al., 2008 ).
Cadherin clustering also required binding of p120-catenin and β-catenin
to cadherin juxtamembrane region and cytoplasmic tail, respectively. p120-
catenin is essential for the retention of cadherins at the plasma membrane.
Studies using siRNA to knockdown p120-catenin or by overexpressing
exogenous cadherins have shown that p-120 catenin-cadherin association
is able to stabilize the cadherins by preventing cadherins at the cell surface
from being internalized and degraded ( Davis et al., 2003 ; Iyer et al., 2004 ;
Maeda et al., 2006 ). On the other hand, β-catenin-cadherin association
promotes cadherin clustering by connecting cadherins to actin cytoskele-
ton through the adaptor α-catenin, which can bind β-catenin and also actin
filaments ( Harris and Tepass, 2010 ; Yonemura, 2011 ). Studies have shown
that during formation of AJs which is initiated by nectins, clustering of
cadherins is aided by remodeling of actin cytoskeleton via actin regulat-
ing proteins such as the Arp2/3 complex which induces branched actin
polymerization for capturing clusters of cadherins ( Kametani and Takeichi,
2007 ; Le Clainche et al., 2007 ; Sato et al., 2006 ). However, a disruption of
cortical actin filaments can lead to dissolution of cadherins at the cell-cell
interface ( Quinlan and Hyatt, 1999 ), illustrating the importance of actin
filament network in recruiting cadherin-based AJs to cell-cell interface.
It was long believed that AJs were maintained through the association of
cadherin-β-catenin-α-catenin complex to actin filaments. However, it is
now known that α-catenin cannot simultaneously bind to β-catenin and
actin, implying a cadherin-β-catenin-α-catenin-actin association does not
exist ( Drees et al., 2005 ). Instead, α-catenin exists as monomers and dimers,
which bind to β-catenin and actin, respectively. Clustering of cadherin-
β-catenin-α-catenin complex during AJ formation induces a localized