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 303

in which the members have a lower polypeptide sequence similarity, includes
CAR, JAM-D ( JAM-4) and JAM-like ( JAM-L). Herein, we focus on the for-
mer subfamily since its members have been better characterized and studied
in the testis. JAMs differ from claudins and occludin topologically since each
JAM molecule has only one extracellular domain, a single transmembrane
region and a cytoplasmic tail that varies in length among different isoforms
( Mandell and Parkos, 2005 ; Severson and Parkos, 2009 ). Unlike claudins and
occludin, JAMs alone is insufficient to from TJ strands as no TJs were detected
in many primary cultures of fibroblasts and established fibroblast cell lines that
expressed either JAM-A or JAM-C. However, JAMs are concentrated to the
TJs when examined by immunofluorescence microscopy ( Morris et al., 2006 ).
JAMs are also distributed in and around TJ strands under electron microscopy,
indicating their intimate association with the TJ barrier ( Itoh et al., 2001 ).
The involvement of JAM proteins in TJ-barrier function has been revealed
in several studies. For instance, a study in T84 human intestinal epithelial cells
using anti-JAM-A antibody has shown that JAM-A is necessary for recov-
ery of Ca 2+ depletion-induced TJ-barrier disruption as re-establishment of
TJ barrier was disrupted due to the loss of JAM-A and occludin function
following antibody treatment ( Liu et al., 2000 ). JAMs are also required for the
resealing of a disrupted TJ barrier induced by treatment of epithelial cells with
synthetic peptides corresponding to the extracellular domain of JAMs ( Liang
et al., 2000 ). Moreover, a leaky TJ-permeability barrier was found in the intes-
tinal epithelial cells of JAM-A knockout mice, indicating the significance of
JAM proteins in barrier function ( Laukoetter et al., 2007 ). Interestingly, such
leaky TJ barrier might be the result of an induction of claudin-10 and -15
detected in the intestinal epithelial cells obtained from JAM-A knockout mice
versus the wild-type. It was shown that an induction of certain claudins would
lead to an increase in permeability of certain ions across the TJ barrier ( Lau-
koetter et al., 2007 ). An induction of claudins after knockout of JAM-A and a
down-regulation of occludin after JAM-A antibody treatment thus illustrate
that JAMs may regulate the TJ barrier by altering the localization and/or
expression of other TJ proteins ( Severson and Parkos, 2009 ). Regardless of
the importance of JAMs in modulating the barrier function in cell lines or
intestinal epithelia, the significance of JAMs to the BTB remains unknown.
Although JAM-A and JAM-B are found in the BTB ( Morrow et al., 2010 ),
deletion of JAM-A or homozygous mutation of JAM-B had no impact on the
BTB integrity ( Sakaguchi et al., 2006 ; Shao et al., 2008 ). It is known that mice
with JAM-A deleted or JAM-B mutated remained fertile and their seminifer-
ous epithelium was histologically normal ( Sakaguchi et al., 2006 ; Shao et al.,