Connexins are phylogenetically very old integral membrane proteins and function, among other things, as structural proteins in the hexamer structures of gap junctions. Intercellular communication via gap junctions allows cells to respond synchronously to different intercellular signals by regulating the influx and efflux of small molecules (< 1000 Da) and ions between the cytoplasms of neighboring cells. In the skin, gap junctions are involved in the coordination of growth and differentiation of keratinocytes, among other things (see Cell contacts below).
To date, more than 30 different connexins have been described in vertebrates. The most important connexins in human skin are connexin 43 (Cx43) and connexin 26 (Cx26). Cx43 is mainly expressed in the cells of the suprabasal layers and is considered the major gap junction subunit of the interfollicular epidermis. Cx26 is expressed especially in hair follicles and sweat glands and is considered a regulator of keratinocyte homeostasis during rapid growth or differentiation.
Mutations in the gene encoding connexin-26 (GJB2 gene) lead to functional disorders of the inner ear (syndromal or non-syndromal deafness).
Disease patterns associated with expression of defective connexins (Avshalumova L et al. 2015):
- Erythrokeratodermia figurata variabilis (Mendes da Costa syndrome; mutations in connexin 31).
- Hidrotic ectodermal dysplasia (Clouston syndrome; connexin 30).
- Erythrokeratodermia progressiva, Burns type
- Keratosis palmoplantaris with mutations in connexin 26
- Bart-Pumphrey syndrome (connexin 26)
- Palmoplantar keratosis with deafness (connexin 26)
- Keratitis-ichthyosis-deafness syndrome (KID syndrome) (connexin 26)
- Keratosis palmoplantaris mutilans Vohwinkel