Biology Reference
In-Depth Information
(T84) cell cultures has shown that the occludin peptide-induced TJ-barrier
disruption was mediated by redistribution of other TJ proteins (e.g. claudin-1)
and TJ adaptor (e.g. ZO-1) (
Nusrat et al., 2005
), illustrating occludin may act
as a “signaling” regulatory TJ protein. More important, the use of monoclonal
antibody against the second extracellular loop of occludin in T84 cells was
found to disrupt epithelial cell polarity but not the TJ barrier (
Tokunaga et al.,
2007
). Collectively, these findings illustrate the complex functional role of
occludin at the TJ barrier, supporting the notion of its species- and/or tissue-
specific function regarding its involvement in TJ-barrier formation and main-
tenance. Nonetheless, these findings illustrate that occludin, unlike claudins,
may have other role(s) and serving as a signaling molecule in controlling the
permeability in TJs, such as fine-tuning the barrier function, besides serving as
the building block of TJs in some epithelia. This notion is also supported by
studies illustrating that overexpression of exogenous occludin in fibroblasts was
able to induce the formation of TJ strands, but these TJ strands were shorter
and lesser in quantity when compared to those claudin-based TJ strands; and
when fibroblasts were co-transfected with occludin and claudins, occludin was
recruited to the TJ strands formed by claudins, and together they formed con-
tinuous belt-like ultrastructures at the cell-cell interface, which was in con-
trast to the punctuate pattern when occludin was overexpressed alone (
Furuse
et al., 1998
). More important, while young adult occludin knockout mice at
6-10 weeks of age were fertile but when these mice reached adulthood by
>30 weeks, besides being infertile with seminiferous tubules were found to be
devoid of spermatocytes and spermatids, calcification in the brain, and chronic
gastritis in the gastric epithelium were detected (
Saitou et al., 2000
), illustrat-
ing occludin, and perhaps TJs, may be playing more important cellular roles
besides serving as an indispensable protein at the TJ barrier. In this context,
it is of interest to note that studies have reported internalization of occlu-
din by caveolae and/or clathrin-mediated endocytosis (
Murakami et al., 2009
;
Schwarz et al., 2007
;
Shen and Turner, 2005
), including the Sertoli cell TJ bar-
rier (
Wong et al., 2009
;
Yan et al., 2008c
), illustrating occludin can be rapidly
mobilized to other cellular domains to exert its function besides the TJ barrier.
2.1.3. Junctional Adhesion Molecules
JAMs are members of the immunoglobulin superfamily (IgSF) proteins; the
extracellular region of these TJ-integral membrane proteins possess two Ig-
like domains. Based on sequence homology, JAM family is composed of two
subfamilies with one of them comprises three closely related members namely
JAM-A ( JAM-1), JAM-B ( JAM-2) and JAM-C ( JAM-3). Another subfamily,
Search WWH ::
Custom Search