| Literature References | 1. TSUKITA, S. AND FURUSE, M.
Overcoming barriers in the study of tight junction functions: from occludin
to claudin.
GENES CELLS 3 569-573 (1998).
2. TSUKITA, S. AND FURUSE, M.
Occludins and claudins in tight-junction strands: leading or supporting
players?
TRENDS CELL BIOL. 9 268-273 (1999).
3. ITOH, M., NAHAFUCHI, A., MOROI, S. AND TSUKITA, S.
Involvement of ZO-1 in cadherin-based cell adhesion through its direct
binding to alpha catenin and actin filaments.
J.CELL BIOL. 138 181-192 (1997).
4. ITOH, M., FURUSE, M., MORITA, K., KUBOTA, K., SAITOU, M. AND TSUKITA S.
Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and
ZO-3, with the COOH termini of claudins.
J.CELL BIOL. 147 1351-1363 (1999).
5. FANNING, A., JAMESON, B., JESAITIS, L. AND ANDERSON, J.
The tight junction protein ZO-1 establishes a link between the transmembrane
protein occludin and the actin cytoskeleton.
J.BIOL.CHEM. 273 29745-29753 (1998).
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| Documentation | Zona occludens (ZO), or tight junctions (TJ), are specialised membrane
domains found at the most apical region of polarised epithelial and endo-
thelial cells that create a primary barrier, preventing paracellular
transport of solutes, and restricting the lateral diffusion of membrane
lipids and proteins, thus maintaining cellular polarity [1]. Under freeze-
fracture electron microscopy, TJs appear as a network of continuous
anastomosing intramembranous strands. These strands consist mainly of
claudins and occludin, which are transmembrane proteins that polymerise
within plasma membranes to form fibrils [2].
The zona occludens proteins (ZO-1, ZO-2 and ZO-3) are a family of TJ-
associated proteins that function as cross-linkers, anchoring the TJ strand
proteins to the actin-based cytoskeleton [3,4]. Each protein contains three
PDZ (postsynaptic density, disc-large, ZO-1) domains, a single SH3 (Src
Homology-3) domain and a GK (guanylate kinase) domain, the presence of which
identifies them as members of the membrane-associated guanylate kinase
(MAGUK) protein family. They also share an acidic domain at the C-terminal
region of the molecules not found in other MAGUK proteins. It has been
demonstrated that the first PDZ domain is involved in binding the C-terminal
-Y-V motif of claudins [4]. By contrast, the occludin-binding domain of
ZO-1 has been shown to lie in the GK and acidic domains [5]. Although the
precise location of the actin-binding motif has not been elucidated, it
appears to be within the C-terminal half of the molecules, since
transfection of this region into fibroblasts induces co-localisation
of ZO-1 and ZO-2 with actin fibres [5].
ZONOCCLUDNS is a 4-element fingerprint that provides a signature for the
zona occludens protein family. The fingerprint was derived from an initial
alignment of 10 sequences: the motifs were drawn from conserved regions
spanning virtually the full alignment length - motif 1 lies between the
first and second PDZ domain; motif 2 resides between the SH3 and the GK
domain; and motif 3 lies beyond the GK domain in the C-terminal portion of
the alignment. A single iteration on SPTR39_22_17.3f was required to reach
convergence, no further sequences being identified beyond the starting set.
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