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 310

c-Src in an afadin-independent manner ( Fukuyama et al., 2005 ; Kawakatsu
et al., 2005 , 2002 ). Activated Cdc42 and Rac, in turn, trigger reorgani-
zation of actin cytoskeleton through the actin-binding protein IQGAP1,
which induce branched actin polymerization via the Arp2/3 complex ( Le
Clainche et al., 2007 ; Sato et al., 2006 ) to recruit cadherins to the site. It is
noted that at this step, the recruited cadherins are non- trans -interacting since
they have yet to associate with cadherins from neighboring cells. Clustering
of these non- trans -interacting cadherins is then assisted by afadin-associated
trans -interacting nectins. This is achieved by activation of Rap1 by trans -
interacting nectins, activated Rap1 then associates with afadin to form a
complex, which in turn binds to p120-catenin to retain cadherins at plasma
membrane ( Hoshino et al., 2005 ; Sato et al., 2006 ). Hence, localized cluster-
ing of cadherins takes place which favors the trans -interaction of cadherins
to establish AJs.
Nectin-2 is expressed in rodent Sertoli cells ( Bouchard et al., 2000 ;
Ozaki-Kuroda et al., 2002 ). Mice lacking nectin-2 are infertile illustrating
nectin-2 is indispensable for spermatogenesis ( Bouchard et al., 2000 ; Ozaki-
Kuroda et al., 2002 ). Although studies of mice lacking nectin-2 were focused
on apical ES ( Kawakatsu et al., 2002 ) or spermatids ( Bouchard et al., 2000 ),
it was noted that the actin filament bundles at the apical ES in these mice
were absent, suggesting that their BTB might have been disrupted due to a
disorganized actin cytoskeleton.
2.2.1.3. Interplay between AJs and TJs Via Adaptor Proteins
As noted above, cell adhesion molecules cross talk with each other via their
peripheral adaptors to maintain epithelial homeostasis. For instance, AJs are
crucial for TJ assembly, and ZO-1 is a crucial player in this process ( Hartsock
and Nelson, 2008 ; Sakisaka et al., 2007 ). Studies have shown that nectin-afa-
din complex is able to recruit ZO-1, which was then used to recruit JAMs,
claudins and occludin to the apical junctional complex to form TJs ( Ooshio
et al., 2010 ; Yokoyama et al., 2001 ). The necessity of trans -interacting nectins
in the establishment of TJs was demonstrated when such interaction was
blocked via the use of a chimeric protein that bound to the extracellular
region of nectins, the recruitment of JAMs ( Fukuhara et al., 2002a ), claudins
and occludin ( Fukuhara et al., 2002b ) for TJ assembly was impaired. Moreover,
the importance of trans -interacting nectin-afadin association in initiating TJ
assembly was shown by expressing nectins with a truncated C-terminus,
rendering nectins incapable of binding to afadin, leading to an impairment
to recruit ZO-1 to establish TJs ( Yokoyama et al., 2001 ). Furthermore,