Abstract：
:Gap junctions and hemichannels comprised of connexins influence epidermal proliferation and differentiation. Significant advances in our understanding of the functional role of connexins in the skin have been made by studying the diseases caused by connexin mutations. Eleven clinically defined cutaneous disorders with an overlapping spectrum of phenotypes are caused by mutations in five different connexin genes, highlighting that disease presentation must be deciphered with an understanding of how connexin functions are affected. Increasing evidence suggests that the skin diseases produced by connexin mutations result from dominant gains of function. In palmoplantar keratoderma with deafness, the connexin 26 mutations transdominantly alter the function of wild-type connexin 43 and create leaky heteromeric hemichannels. In keratitis-ichthyosis-deafness syndrome, different connexin 26 mutations can either form dominant hemichannels with altered calcium regulation or increased calcium permeability, leading to clinical subtypes of this syndrome. It is only with detailed understanding of these subtle functional differences that we can hope to create successful pathophysiology driven therapies for the connexin skin disorders.
journal_name
Semin Cell Dev Bioljournal_title
Seminars in cell & developmental biologyauthors
Lilly E,Sellitto C,Milstone LM,White TWdoi
10.1016/j.semcdb.2015.11.018subject
Has Abstractpub_date
2016-02-01 00:00:00pages
4-12eissn
1084-9521issn
1096-3634pii
S1084-9521(15)30009-4journal_volume
50pub_type
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