Tj Functions

Cell adhesion to adjacent cells and the extracellular matrix is key not only to the organisation of epithelium into a tissue but also to the regulation of cellular processes such as gene expression, differentiation, motility, and growth (111). Cell adhesion molecules, transmembrane receptors, and cytoskeletal all of which are organised into multimolecular complexes and the activation of signalling pathways, mediate these regulatory functions.

Five main functions are ascribed to the TJ:

(1) The TJ seals the intercellular space and is responsible for the separation of apical and basolateral fluid compartments of epithelia and endothelia. Macromolecules of radii >15 angstroms cannot pass. However, such barriers regulate the passage of small ions etc.

(2) The TJ functions as a diffusion barrier to plasma membrane lipids and proteins, which helps to define apical and basolateral membrane domains of these polarised epithelial and endothelial cells. Therefore the TJ is crucial for the epithelium to generate chemical and electrical gradients across the cell monolayer that is necessary for vectorial transport processes such as absorption and secretion.

(3) TJ molecules act as intermediates and transducers in cell signalling, thus playing a role in the processes of polarity, cell differentiation, cell growth, and proliferation.

(4) TJ proteins act as cell-cell adhesion molecules.

(5) The TJ functions as a barrier to cell migration.

Studies suggest that some of the cell adhesion and cytoskeletal proteins may subserve an additional and important function, namely, suppression of the malignant phenotype of cells in tumorigenesis (111). Whilst the barrier and fence functions of TJs have been well appreciated, it is only recently that concept of the TJ as a complex, multiprotein structure with roles in other cellular processes such as cell polarity, proliferation, and differentiation has been recognised (68). Moreover, it is becoming increasingly clear that the development of human cancer is frequently associated with the failure of epithelial cells to form TJs and to establish correct apicobasal polarity (112).

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