Pamela Cowin

Plakoglobin: A protein common to different kinds of intercellular adhering junctions

We have established, by means of a monoclonal antibody and a cDNA clone, that a desmosomal polypeptide of Mr 83,000 also occurs at the plaques of other types of adhering junctions, including the vinculin-actin-associated intercellular junctions, e.g., the zonula adhaerens of epithelial cells and the endothelial, lens, and Sertoli cell junctions. This is the first component found in common among otherwise biochemically distinct plaque domains. Despite its concentration at these intercellular junctions, it is absent from the respective cell-substratum contact sites. In addition, it appears in a globular soluble 7S form in the cytoplasm. We discuss the significance of this protein, for which the name plakoglobin is proposed, in terms of its interaction with such biochemically diverse membrane domains and their different types of associated cytoskeletal filaments.

The Endothelial Junction

The endothelium of most blood vessels is a single layer of tightly packed cells which line the vascular lumen and border on the basal lamina and, in some arteries and arterioles, on the processes of vascular smooth muscle cells. Like singlelayered epithelia, the endothelial cells are polar, with an apical, i.e., adluminal, and a basal, i.e., abluminal, plasma membrane region which appear to be segregated from each other by a special membrane region containing occluding, i.e., “tight,” junctions (for reviews see Ref. 89). Again similarly to polar epithelia, the endothelium is capable of vectorial sorting, secretion, and virus budding as well as endocytotic and transcytotic processes (for examples see Refs. 47,66,72). Obviously, tight sealing of endothelial cells to each other is a prerequisite for their physiological functioning, and situations in which the coherence of the endothelial layer is locally and/or transiently interrupted are usually associated with pathological processes (e.g., Refs. 16,17,52,54,77,86,92). The elucidation of the molecular organization of the “endothelial junction” is crucial to our understanding of the structures and molecules involved in the intercellular adhesion of the endothelial cells. This junctional zone is characterized by a relatively close apposition of the adjacent plasma membranes which are flanked by a so-called “parajunctional zone” of cortical cytoplasm (for definition see Ref. 90). So far only two specific junctions have been identified within this junctional complex. These are the occluding (tight) and the communicating (gap) junctions which are morphologically similar to those present in other tissues (reviewed in Refs. 89-92; for certain freeze-cleave aspects see also Refs. 98,110). Typical desmosomes or other adhering junction structures have not been demonstrated in higher vertebrates. However, Fawcett29,30 has attracted attention to

Maintenance of desmosomes in mouse hepatocytes after drug-induced rearrangement of cytokeratin filament material. Demonstration of independence of desmosomes and intermediate-sized filaments

The distribution of desmosomes and cytokeratin filaments (tonofilaments) in hepatocytes of normal mice and those intoxicated with griseofulvin was studied by immunofluorescence microscopy. Treatment with griseofulvin over prolonged periods of time resulted in the dissociation of cytokeratin filaments from the plasma membrane and the inclusions of cytokeratin material in typical cytoplasmic aggregates, i.e. Mallory bodies. However, such hepatocytes still displayed typical desmosomal arrays, including rather regularly spaced desmosomes along the bile canaliculi. These observations show that, in this tissue, desmosomes are able to maintain their characteristic positions along the plasma membrane after disconnection of the intermediate filament cytoskeleton. This indicates that maintenance of desmosomal integrity and position is independent of desmosome anchorage to tonofilaments. The results are discussed in relation to current concepts of desmosome formation and turnover.

The Desmosomal Domain, An Example of Cell-Cell as well as Membrane-Cytoskeleton Interaction

Desmosomes are intercellular junctions characterized by (1) a midline structure containing carbohydrate residues of glycoproteins, (2) the membrane proper, and (3) a cytoplasmic plaque which is insoluble in low and high salt buffers, non-denaturing detergents and thiol agents and is remarkably resistant to treatment with chaotropic and denaturing agents. Major polypeptides of this plaque structure have been characterized by biochemical and both conventional and monoclonal immunological methods. They contain one or two predominant non-glycosylated polypeptides, desmoplakins I (M 250K) and II (M 215K) of almost neutral isoelectric pH, which are closely relateS to each other and have been fairly well conserved in diverse epithelia and during evolution. In addition, at least in epidermis, the plaques contain a non-glycosylated polypeptide of M 83K (“band 5”) isoelectric with serum albumin and non-glycosylated basic polypeptide of M 75K (“band 6”). The latter two polypeptides have been identified as translational products of epidermal mRNA. Guinea pig antibodies and monoclonal murine antibodies to such plaque proteins have detected similar antigens in epithelial, arachnoidal and myocardial cells, including Purkinje fibre cells of the heart, as well as in tumors derived from epithelial cells, notably carcinomas.