Desmosomal cadherins, including the desmocollin family members and desmogleins, are found atdesmosome cell-cell junctions and are required forcell adhesion and desmosome formation via interactions with their extracellularcadherin regions.[13] Desmosomes function to anchorintermediate filaments at sites of strong adhesion, which undergo high mechanical stress, such as incardiac muscle.[14]Desmocollins are integral components to desmosomes and studies have shown that in addition to tensile strength, desmocollins also function as molecular sensors and facilitators ofsignal transduction.[15] Studies in zebrafish expressing a mutant desmocollin-2 have shed light on its function in themyocardium as a pivotal component for normal myocardial structure and function. Knockdown of desmcollin-2 caused malformations in desmosomal plaques andbradycardia, dilation of the ventricular chamber and reducedfractional shortening.[16]
Hallmark features of ARVC include enlargement of theright ventricle, replacement of right ventricularcardiomyocytes with fibrofatty deposits,electrocardiographic abnormalities, andarrhythmias.[29][30][31][32] Biopsies from patients with ARVC consistently show abnormalities inintercalated discs, with decreased numbers ofdesmosomes and widening of intercellular gaps between adjacent cardiomyocytes, suggesting that this disease is a disease of intercalated discs.[33][34] Studies investigating two heterozygousDSC2 mutations have shown that certain mutations in theN-terminal region can modify the subcellular localization of desmocollin-2 from the desmosomal plaque to thecytoplasm.[35]
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^abGreenwood MD, Marsden MD, Cowley CM, Sahota VK, Buxton RS (September 1997). "Exon-intron organization of the human type 2 desmocollin gene (DSC2): desmocollin gene structure is closer to "classical" cadherins than to desmogleins".Genomics.44 (3):330–5.doi:10.1006/geno.1997.4894.PMID9325054.
^abTroyanovsky RB, Chitaev NA, Troyanovsky SM (December 1996). "Cadherin binding sites of plakoglobin: localization, specificity and role in targeting to adhering junctions".Journal of Cell Science. 109 ( Pt 13) (13):3069–78.doi:10.1242/jcs.109.13.3069.PMID9004041.
^Nuber UA, Schäfer S, Schmidt A, Koch PJ, Franke WW (January 1995). "The widespread human desmocollin Dsc2 and tissue-specific patterns of synthesis of various desmocollin subtypes".European Journal of Cell Biology.66 (1):69–74.PMID7750520.
^Dusek RL, Godsel LM, Green KJ (January 2007). "Discriminating roles of desmosomal cadherins: beyond desmosomal adhesion".Journal of Dermatological Science.45 (1):7–21.doi:10.1016/j.jdermsci.2006.10.006.PMID17141479.
^Green KJ, Gaudry CA (December 2000). "Are desmosomes more than tethers for intermediate filaments?".Nature Reviews. Molecular Cell Biology.1 (3):208–16.doi:10.1038/35043032.PMID11252896.S2CID20348206.
^van Tintelen JP, Hofstra RM, Wiesfeld AC, van den Berg MP, Hauer RN, Jongbloed JD (May 2007). "Molecular genetics of arrhythmogenic right ventricular cardiomyopathy: emerging horizon?".Current Opinion in Cardiology.22 (3):185–92.doi:10.1097/HCO.0b013e3280d942c4.PMID17413274.S2CID24552922.
^Groeneweg JA, van der Zwaag PA, Jongbloed JD, Cox MG, Vreeker A, de Boer RA, van der Heijden JF, van Veen TA, McKenna WJ, van Tintelen JP, Dooijes D, Hauer RN (Apr 2013). "Left-dominant arrhythmogenic cardiomyopathy in a large family: associated desmosomal or nondesmosomal genotype?".Heart Rhythm.10 (4):548–59.doi:10.1016/j.hrthm.2012.12.020.PMID23270881.
^Bauce B, Nava A, Beffagna G, Basso C, Lorenzon A, Smaniotto G, et al. (January 2010). "Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia".Heart Rhythm.7 (1):22–9.doi:10.1016/j.hrthm.2009.09.070.PMID20129281.
^Lahtinen AM, Lehtonen E, Marjamaa A, Kaartinen M, Heliö T, Porthan K, et al. (August 2011). "Population-prevalent desmosomal mutations predisposing to arrhythmogenic right ventricular cardiomyopathy".Heart Rhythm.8 (8):1214–21.doi:10.1016/j.hrthm.2011.03.015.PMID21397041.
^Al-Sabeq B, Krahn AD, Conacher S, Klein GJ, Laksman Z (June 2014). "Arrhythmogenic right ventricular cardiomyopathy with recessive inheritance related to a new homozygous desmocollin-2 mutation".The Canadian Journal of Cardiology.30 (6): 696.e1–3.doi:10.1016/j.cjca.2014.01.014.PMID24793512.
^Garcia-Pavia P, Syrris P, Salas C, Evans A, Mirelis JG, Cobo-Marcos M, et al. (November 2011). "Desmosomal protein gene mutations in patients with idiopathic dilated cardiomyopathy undergoing cardiac transplantation: a clinicopathological study".Heart.97 (21):1744–52.doi:10.1136/hrt.2011.227967.PMID21859740.S2CID15172565.
^McNally, E.; MacLeod, H.; Dellefave-Castillo, L.; Adam, M. P.; Ardinger, H. H.; Pagon, R. A.; Wallace, S. E.; Bean LJH; Mirzaa, G.; Amemiya, A. (1993). "Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy".GeneReviews.PMID20301310.
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