Abstract
Gap junctions are small membrane pores that facilitate rapid intercellular communication in all vertebrate cells, and are composed of connexins. In humans, 21 different connexin genes are expressed. Each tissue has its own expression pattern. Gap junctions are particularly prominent in the skin and mutations in skin-expressed connexins cause a broad spectrum of ectodermal dysplasias. Intriguingly, it has been found that different dominant mutations in a single skin-expressed connexin, connexin 26, cause a wide variety of syndromes, pointing to great underlying functional complexity that we are now beginning to dissect. Important steps have been taken towards understanding the underlying biology of gap junction disorders of the skin, but how connexin mutations cause skin disease is still essentially unknown. Aberrant connexin function is seen in hyperproliferative skin diseases, such as skin cancer, psoriasis and delayed wound healing in diabetic skin. Thus, being able to modulate gap junction activity might be desirable for therapy. A thorough understanding of gap junctions is, therefore, a pertinent biomedical goal. With this review, we aim to provide a comprehensive overview of all mutations in the different skin-expressed connexin genes that cause a skin phenotype. We discuss the clinical aspects, molecular background and current investigations of the authors work and also indicate future directions for research.
Financial & competing interests disclosure
Eugene de Zwart-Storm is supported by a GENESKIN grant and the ESRF New Investigator Award 2009. This work is supported by the Foundation for Ichthyosis and Related Skin Types (F.I.R.S.T.) and the Stichting de Drie Lichten. Maurice van Steensel is supported by grants from the Netherlands Organization for Scientific Research ZONMW (grant 907-00-202), the Dutch Cancer Society (grant UM 2009-4352), the GROW research school for oncology and developmental biology and the Maastricht University Medical Center. Patricia Martin is supported by grants from the Chief Science Office (CZB/4/606) and British Skin Foundation (S307). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.