The Cardiac Desmosome and Arrhythmogenic Cardiomyopathies

Cortactin Is Required for N-cadherin Regulation of Kv1.5 Channel Function

“…A high resolution image of the site of end-end contact between cardiomyocytes reveals an electron-dense organization called the intercalated disc (ICD). 2 Its classic definition involves three structures: adherens junctions and desmosomes, providing mechanical coupling; and gap junctions, providing electrical coupling (3,4). N-cadherin is the primary cell adhesion molecule responsible for maintaining the ICD structure as it interacts intracellularly with catenins, which mediate linkage to the actin cytoskeleton (5,6).…”

Intercellular Connections in the Heart: The Intercalated Disc

“…First identified as adhesive structures of epithelial cells by Giulio Bizzozero in the late 19 th century, the term desmosomes was initially coined in 1920 by Josef Schaffer from the Greek words "desmo" and "soma" meaning bond or fastening and body, respectively; (reviewed in Delva et al, 2009). In the middle of the 20 th century, desmosomes were identified as a major component of the cardiac ID (Fawcett and McNutt, 1969;Grimley and Edwards, 1960;Muir, 1957;Sjostrand and Andersson, 1954), where its main function is to provide structural support to neighboring cardiomyocytes (reviewed in Delmar and McKenna, 2010;Delva et al, 2009;Thomason et al, 2010). Desmosomes bring apposing cells within 20-35 nm of each other (Noorman et al, 2009), and are typically found in close proximity to gap junctions, although recent studies indicate that they are also present next to adherens junctions within the area composita.…”

“…Its clinical manifestations include ventricular arrhythmias, syncope, heart failure and sudden cardiac death (Delmar and McKenna, 2010;Estigoy et al, 2009;Lombardi and Marian, 2011). ARVC has an estimated prevalence of 1 in 5,000 (SenChowdhry et al, 2010), although in some regions (e.g.…”

“…Alterations in the amounts, localization and functional properties of desmosomal proteins not only affect intercellular adhesion, but also promote remodelling of gap junctions by leading to abnormal expression and distribution of gap junctional proteins, and primarily connexin-43, which in turn induces defects in the electrochemical coupling of neighbouring cardiocytes and leads to the development of severe arrhythmias (Kaplan et al, 2004a;Pieperhoff et al, 2008;Saffitz, 2009). On the contrary, changes in gap junctions do not affect the structural integrity or proper function of desmosomes and adherens junctions, and thus mechanical coupling of adjacent cardiocytes is not disrupted (Delmar and McKenna, 2010;Li and Radice, 2010;Noorman et al, 2009). A number of mutations have also been identified in the gene encoding connexin-43, which are associated with the development of oculodentodigital dysplasia (ODDD) that is frequently accompanied by hair and skin defects, too (Kelly et al, 2006).…”

“…Although, the ID has been traditionally described to contain three distinct structures (i.e. gap junctions, adherens junctions and desmosomes), recent technological advancements indicate that they are more interwined than originally proposed (Delmar and McKenna, 2010). Consistent with this, adherens junctions and desmosomes are intimately associated in the "area composita" where proteins from both structures are present Franke et al, 2006).…”