Insights into Desmosome Biology from Inherited Human Skin Disease and Cardiocutaneous Syndromes. (June 2014)

• Record Type: Journal Article
• Authors: Nitoiu, Daniela; Etheridge, Sarah L.; Kelsell, David P.
• Is Part Of: Cell communication & adhesion. Volume 21:Number 3(2014)
• Page Start: 129
• Page End: 140
• Publication Date: 2014-06
• Subjects: Cell adhesion -- Periodicals; Cell interaction -- Periodicals; Cellular signal transduction -- Periodicals; 571.6
• DOI: 10.3109/15419061.2014.908854
• Languages: English
• ISSNs: 1541-9061

Abstract

<abstract> <title>Abstract</title> <p>The importance of desmosomes in tissue homeostasis is highlighted by natural and engineered mutations in desmosomal genes, which compromise the skin or heart and in some instances both. Desmosomal gene mutations account for 45–50% of cases of arrhythmogenic right ventricular cardiomyopathy, and are mutated in an array of other disorders such as striate palmoplantar keratoderma, hypotrichosis with or without skin vesicles and lethal acantholytic epidermolysis bullosa. Recently, we reported loss-of-function mutations in the human <italic>ADAM17</italic> gene, encoding for the 'sheddase' ADAM17, a transmembrane protein which cleaves extracellular domains of substrate proteins including TNF-α, growth factors and desmoglein (DSG) 2. Patients present with cardiomyopathy and an inflammatory skin and bowel syndrome with defective DSG processing. In contrast, the dominantly inherited tylosis with oesophageal cancer appears to result from gain-of-function in <italic>ADAM17</italic> due to increased processing via iRHOM2. This review discusses the heterogeneity of mutations in desmosomes and their regulatory proteins.</p> </abstract>