Insights into the Role of Cell–Cell Junctions in Physiology and Disease - International Review of Cell and Molecular Biology - page 198

Figure 5.2 One hypothesis for the function of plakoglobin in disease is that plakoglobin
may participate in a Wnt pathway to regulate signaling and apoptosis. (A) A simplified
model of the canonical Wnt/b-catenin pathway shows that normally, Wnt signaling
leads to b-catenin translocation into the nucleus, where it acts in conjunction with
TCF/LEF to activate specific target genes. In contrast, plakoglobin is normally confined
to the desmosomes and adherens junctions. (B) When cell cell junctional structures are

disrupted, plakoglobin translocates into the nucleus, where it displaces b-catenin. The
plakoglobin-TCF/LEF complex ultimately results in cell apoptosis through mechanisms
that are yet to be elucidated.

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progression, including its apparently variable penetrance and the potential
influence of mechanical stresses in modulating the condition.

4.2.3 Tight junctions
Tight junctions play key roles in the kidney, ear, and liver, among other tis-
sues ( Aijaz et al., 2006; Furuse, 2010 ). Broad classes of disease are associated
with tight junctions. One identifiedmutation, in the human claudin 16 gene,
is associated with a rare autosomal-recessive renal disorder, familial hypo-
magnesemia with hypercalciuria and nephrocalcinosis ( Simon et al., 1999;
Weber et al., 2001 ). A claudin 1 gene mutation was found to cause neonatal
ichthyosis and sclerosing cholangitis, demonstrating claudin's role in human
skin and liver physiology ( Baala et al., 2002; Furuse et al., 2002; Hadj-Rabia
et al., 2004 ). Certain mutations in the claudin 14 gene result in cochlear hair
cell degeneration and cause autosomal-recessive deafness disorder DFNB29