Tj Molecular Structure

The TJ has a characteristic structure, appearing as discrete sites of fusion between the outer plasma membrane of adjacent cells when viewed in ultrathin section electron microscopy. When visualised using freeze-fracture, they appear as continuous intramembrane particle strands in the protoplasmic face with complimentary grooves in the extracellular face (22). These completely circumscribe the apices of the cells as a network of intramembrane fibrils (4) appearing as a series of "kissing" points (Figure 2).

Figure 2. Distribution of TJs at the apical membranes (left) forming a series of "kissing" points (Right).

This ultrastructure is representative of the conglomerate of molecules that constitute, associate with or regulate TJs (23), Figure 3. Although a number of proteins were identified in the mid-1980s, the list of additional molecules has expanded considerably over recent years (Table 1). The molecular components of the TJ have been extensively investigated (3, 24) and it became apparent that the junctions could be reasonably separated into three regions: (i) the integral transmembrane proteins- occludin, clau-dins, nectins, and junctional adhesion molecules (JAM), together with other CTX family members; (ii) the peripheral or plaque anchoring protein, often containing PDZ motifs- zonula occludens (ZO)-1, -2, -3, MAGI-1, etc.; and (iii) TJ-associated/regulatory proteins- a-catenin, cingulin, etc.

Rab Protein Structure

Also rab-13, Ga-2. PKC, aPKC, c-yes. rab 3B, c-src, PAR-6, PILT

Figure 3. Schematic representation of the interactions suggested between proteins involved in TJ structure and function (see text).

Also rab-13, Ga-2. PKC, aPKC, c-yes. rab 3B, c-src, PAR-6, PILT

Figure 3. Schematic representation of the interactions suggested between proteins involved in TJ structure and function (see text).

The integral transmembrane proteins are the essential adhesion proteins responsible for correct assembly of the TJ structure and controlling TJ functions via homotypic and heterotypic interactions. Successful assembly and maintenance of the TJ is accomplished by anchorage of the transmembrane proteins by the peripheral or plaque proteins such as ZO-1 which act as a scaffold to bind the raft of TJ molecules together and provide the link to the actin cytoskeleton and the signalling mechanism of the cell. This is in conjunction with the associated/regulatory proteins.

Table 1. Proteins involved in TJ structure, function and regulation

Integral transmembrane proteins Peripheral plaque proteins Associated proteins

Cingulin, 7H6, Symplekin, ZONAB Rab-13, 19B1, Ponsin Rab 3B, PKC, l-afadin c-src, Gai-2, Gai-12, a-catenin, Pals, PATJ PKA, JEAP, Pilt, PTEN, ZAK, SCRIB, ITCH, Rho-GTPases, WNK4, Vinculin

Occludin Claudins 1-24

Junctional Adhesion Molecules (A-C, 4) and other CTX proteins such as Coxsackie Adenovirus Receptor (CAR) Nectins 1-4 Nectin-like 1-5

Zonula occludens-1 (ZO-1 )

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