Sealing the live part of the skin: the integrated meshwork of desmosomes, tight junctions and curvilinear ridge structures in the cells of the uppermost granular layer of the human epidermis.

In the literature the question of whether a system structurally and functionally related to the barrier function of the tight junctions (TJs) of polarized epithelia exists in the epidermis has been and still is controversially discussed. We have systematically addressed this question in a study of the granular layer of fetal and adult human epidermis, combining different light and electron microscopic methods. We show that the lateral membranes of the cells of the stratum granulosum are connected by an extended subapical complex system integrating desmosomes and TJ structures identified as sites of close membrane-membrane contact and as regions of membrane-to-membrane apposition that in immunoelectron microscopy are positive for TJ marker proteins, notably occludin, indicative of an extended, probably continuous TJ barrier. In addition, we have noted in freeze-fractures of the apical membrane attaching this layer to the basalmost membrane of the stratum corneum an extended system integrating desmosomes with intramembraneous ridge configurations that appear as strands, circles, lariats or complex meshworks showing numerous continuities with the desmosomes. In some regions this system interconnecting desmosomes with curvilinear ridge structures occupies the major part of the plasma membrane. The molecular organizations and possible functional contributions of both structural systems positioned at the border between the living portion of the epidermis and the corneal layer are discussed, in particular in relation to the formation of a stable association between the two layers and of a barrier to the paracellular flow of molecules and particles. It is also discussed whether similar structures occur in other keratinizing stratified squamous epithelia, in squamous metaplasias and in tumors derived from such tissues.