Abstract
In the past decade, an avalanche of findings and reports has correlated arrhythmogenic ventricular cardiomyopathies (ARVC) and Naxos and Carvajal diseases with certain mutations in protein constituents of the special junctions connecting the polar regions (intercalated disks) of mature mammalian cardiomyocytes. These molecules, apparently together with some specific cytoskeletal proteins, are components of (or interact with) composite junctions. Composite junctions contain the amalgamated fusion products of the molecules that, in other cell types and tissues, occur in distinct separate junctions, i.e. desmosomes and adherens junctions. As the pertinent literature is still in an expanding phase and is obviously becoming important for various groups of researchers in basic cell and molecular biology, developmental biology, histology, physiology, cardiology, pathology and genetics, the relevant references so far recognized have been collected and are presented here in the following order: desmocollin-2 (Dsc2, DSC2), desmoglein-2 (Dsg2, DSG2), desmoplakin (DP, DSP), plakoglobin (PG, JUP), plakophilin-2 (Pkp2, PKP2) and some non-desmosomal proteins such as transmembrane protein 43 (TMEM43), ryanodine receptor 2 (RYR2), desmin, lamins A and C, striatin, titin and transforming growth factor-β3 (TGFβ3), followed by a collection of animal models and of reviews, commentaries, collections and comparative studies.
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We thank Werner W. Franke for his encouragement, critical comments and many discussions.
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This work was supported in part by the German Cancer Foundation (Deutsche Krebshilfe, grants 10-2049-Fr1 and 106976 to W.W.F.) and the Federal Ministry for Research and Technology (START-MSC; grant 01GN0942). S.P. thanks, in particular, the German Science Foundation (DFG) for funding of a postdoctoral fellowship (Pi 869/1-1) and the British Heart Foundation (BHF) for subsequent funding within the BHF Centres of Research Excellence (BHF CoRE).
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Rickelt, S., Pieperhoff, S. Mutations with pathogenic potential in proteins located in or at the composite junctions of the intercalated disk connecting mammalian cardiomyocytes: a reference thesaurus for arrhythmogenic cardiomyopathies and for Naxos and Carvajal diseases. Cell Tissue Res 348, 325–333 (2012). https://doi.org/10.1007/s00441-012-1365-0
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DOI: https://doi.org/10.1007/s00441-012-1365-0