Interkeratinocyte Adherens Juncitons: Immunocytochemical Visualization of Cell-Cell Junctional Structures, Distinct from Desmosomes, in Human Epidermis

Abstract

Vinculin and beta-catenin are intracellular attachment proteins linking transmembrane adhesion molecules (E-cadherin) to the actin microfilament cytoskeleton, thus participating in formation of cell-cell adherens junctions, or zonulae adherentes. This type of junction was only recently described in human epidermis due to the imprecise morphological criteria for its recognition. In this study, we investigated the relationship between the expression of the zonula adherens-associated proteins vinculin, beta-catenin, E-cadherin, and actin, on the one hand, and the presence of electron microscopically discernable structures in normal human epidermis on the other. Mouse jejunal epithelium with its orderly arrangement of various junctional structures served as a positive control. Simple and dual post-embedding immunogold labeling was performed on ultrathin sections of Lowicryl K4M and Lowicryl K11M embedded tissues. The overall distribution of the antigens in human epidermis was evaluated on frozen tissue sections using immunofluorescence and laser confocal scanning microscopy. Antibodies against proteins associated with desmosomes (i.e., keratins, desmoglein 1, and plakoglobin) were used as controls. Vinculin and beta-catenin were localized to junctional structures distinct from desmosomes, thus defining the presence of zonulae adherentes. Labeling of actin and E-cadherin was less clearly restricted to the junctions, but these two proteins were also co-expressed at zonulae adherentes and not at desmosomes. In human epidermis, zonula adherens-associated labeling was consistently detected near desmosomes, indicating the possibility of a functional relationship between the two types of junctions.

Protein myozap — a late addition to the molecular ensembles of various kinds of adherens junctions

“…In all these tissues, the myozap-containing AJ-type junctions for the most part appear as fasciae adhaerentes of varying lengths, as whiskers, commata or as dots (puncta adhaerentia) but at present AJs encircling entire cells in a zonula-like mode cannot be totally excluded. Whether these myozap-positive AJ structures include the small AJtype epidermal structures (e.g., Haftek et al 1996;Kaiser et al 1993) remains to be examined in detail. Here, a special topological problem in our studies of the myozapcontaining AJs in interdesmosomal regions of stratified epithelia and squamous carcinomas has been the close vicinity of these junctions and the strand-, whisker-or dot-like junctional structures positive for tight junction (TJ) markers such as occludin and some claudins (e.g., claudins 1 and 4; see also Brandner et al 2002;Furuse et al 2002;Langbein et al 2002Langbein et al , 2003 for reviews see also Schlueter et al 2007;Shin et al 2006;van Itallie and Anderson 2006).…”

Adhesion Receptors in Health and Disease

“…In order to exhibit their adhesion activity, cadherins must form complexes with catenins, which are linked to actin microfilaments (Kaiser et al, 1993). ot-catenins, plakoglobin (y-catenin), r-catenins, and vinculin are cytoplasmic plaque proteins (Kaiser et al, 1993;Haftek et al, 1996). Vinculin is a plaque protein characteristic of the ZA.…”

“…Vinculin is a plaque protein characteristic of the ZA. Recent research has shown that plakoglobin, previously associated with both DS and ZA, is localized only at DS structures (Haftek et al, 1996). The role of ZA in the epidermis is unclear.…”

“…The role of ZA in the epidermis is unclear. It is suggested that the ZA is essential in the control of keratinocyte stratification and participates in DS morphogenesis (Lewis et al, 1994;Haftek et al, 1996). The ZA is also important for the maintenance of normal tissue conformation.…”

Calcium-switch technique and junctional permeability in native rabbit esophageal epithelium

“…Notably lacking on TEM of rabbit EE were structures typical of zonula adherens; these were of importance because of their reported role, along with tight junctions, in establishing the junctional barrier in most epithelia. However, failure to identify zonula adherens on TEM does not exclude their presence, because difficulty distinguishing desmosomes from zonula adherens by TEM has been reported in other stratified squamous epithelium (human epidermis) (14).…”