Internalization of gap junctions in benign familial pemphigus (Hailey-Hailey disease) and keratosis follicularis (Darier's disease)

Hereditary skin disorders involving acantholysis, such as Hailey-Hailey dis ease and Darier's disease, have been genetically linked to distinct chromos omal parts which do not code for known structural proteins. Such evidence s uggests that the genomic abnormalities underlying these dermatoses may conc ern functional/regulatory mechanisms of keratinocyte cohesion. Epidermal co mmunication junctions (gap junctions) are responsible for direct coupling o f cells and, thus, co-ordinate the behaviour of keratinocytes within the ti ssue. Consequently, they remain one of the potential, and poorly studied, e lements in the pathogenesis of hereditary acantholytic diseases. We have in vestigated the distribution and fate of gap junctions during non-immune aca ntholysis, using fine immunolocalization methods at the light and electron microscopic levels. Our results demonstrate normal expression of epidermal gap junction proteins, connexins 2.6 and 43, in non-lesional skin of Hailey -Hailey and Darier's diseases. The gap junctions were not primarily dismant led during acantholysis, typical of both of the studied dermatoses, but und erwent internalization and subsequent cytoplasmic dispersion in the portion s of cells which were no longer attached to the rest of the tissue. In Dari er's disease, perifollicular acantholysis did not specifically concern epit helium of appendages coexpressing connexin 26 in addition to connexin 43, f urther indicating that the observed changes in gap junction localization we re secondary to the loss of cell-cell contact. We demonstrated that the seq uence of changes was identical in both diseases and that the previously des cribed putative differences were apparently related to the degree of acanth olysis present in the studied biopsies. The fate of the junctional structur es and proteins, documented in the present study, is most probably a form o f recycling process also used by normal keratinocytes during organogenesis and tissue differentiation.