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Desmoplakin is Important for Proper Cardiac Cell-Cell Interactions

Published online by Cambridge University Press:  12 December 2011

Stephanie L.K. Bowers ,
William A. McFadden ,
Thomas K. Borg  and
Troy A. Baudino
Stephanie L.K. Bowers
Affiliation:
Department of Medicine, Division of Molecular Cardiology, Texas A&M Health Science Center, Temple, TX 76504, USA
William A. McFadden
Affiliation:
Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, NC, USA
Thomas K. Borg
Affiliation:
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA
Troy A. Baudino*
Affiliation:
Department of Medicine, Division of Molecular Cardiology, Texas A&M Health Science Center, Temple, TX 76504, USA Central Texas Veterans Health Care System, Temple, TX 76504, USA
*
Corresponding author. E-mail: [email protected]
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Abstract

Normal cardiac function is maintained through dynamic interactions of cardiac cells with each other and with the extracellular matrix. These interactions are important for remodeling during cardiac growth and pathophysiological conditions. However, the precise mechanisms of these interactions remain unclear. In this study we examined the importance of desmoplakin (DSP) in cardiac cell-cell interactions. Cell-cell communication in the heart requires the formation and preservation of cell contacts by cell adhesion junctions called desmosome-like structures. A major protein component of this complex is DSP, which plays a role in linking the cytoskeletal network to the plasma membrane. Our laboratory previously generated a polyclonal antibody (1611) against the detergent soluble fraction of cardiac fibroblast plasma membrane. In attempting to define which proteins 1611 recognizes, we performed two-dimensional electrophoresis and identified DSP as one of the major proteins recognized by 1611. Immunoprecipitation studies demonstrated that 1611 was able to directly pulldown DSP. We also demonstrate that 1611 and anti-DSP antibodies co-localize in whole heart sections. Finally, using a three-dimensional in vitro cell-cell interaction assay, we demonstrate that 1611 can inhibit cell-cell interactions. These data indicate that DSP is an important protein for cell-cell interactions and affects a variety of cellular functions, including cytokine secretion.

Keywords

desmoplakincell-cell interactionscardiac cellsdesmosomesfibroblasts
Type
Feature Article
Information
Microscopy and Microanalysis , Volume 18 , Issue 1 , February 2012 , pp. 107 - 114
Copyright
Copyright © Microscopy Society of America 2012

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References

REFERENCES

Asimaki, A., Syrris, P., Ward, D., Guereta, L.G., Saffitz, J.E. & McKenna, W.J. (2009). Unique epidermolytic bullous dermatosis with associated lethal cardiomyopathy related to desmoplakin mutations. J Cutan Pathol 36, 553–559.CrossRefGoogle ScholarPubMed
Banerjee, I., Yekkala, K., Borg, T.K. & Baudino, T.A. (2006). Dynamic interactions between myocytes, fibroblasts and extracellular matrix. Ann NY Acad Sci 1080, 76–84.CrossRefGoogle ScholarPubMed
Baudino, T.A., McFadden, A., Fix, C., Hastings, J., Price, R. & Borg, T.K. (2008). Cell patterning: Interaction of cardiac myocytes and fibroblasts in three-dimensional culture. Microsc Microanal 14, 117–125.CrossRefGoogle ScholarPubMed
Bierkamp, C., Mclaughlin, K.J., Schwarz, H., Huber, O. & Kemler, R. (1996). Embryonic heart and skin defects in mice lacking plakoglobin. Dev Biol 180, 780–785.CrossRefGoogle ScholarPubMed
Borg, K.T., Burgess, W., Terracio, L. & Borg, T.K. (1997). Expression of metalloproteases by cardiac myocytes and fibroblasts in vitro. Cardiac Pathol 6, 261–269.CrossRefGoogle ScholarPubMed
Bowers, S.L.K., Borg, T.K. & Baudino, T.A. (2010). The dynamics of fibroblast-myocyte-capillary interactions in the heart. Ann NY Acad Sci 1188, 143–152.CrossRefGoogle ScholarPubMed
Bullard, T.A., Borg, T.K. & Price, R.L. (2005). The expression and role of protein kinase C in neonatal cardiac myocyte attachment, cell volume and myofibril formation is dependent on the composition of the extracellular matrix. Microsc Microanal 11, 224–234.CrossRefGoogle ScholarPubMed
Camelliti, P., Green, C.R. & Kohl, P. (2006). Structural and functional coupling of cardiac myocytes and fibroblasts. Adv Cardiol 42, 132–149.CrossRefGoogle ScholarPubMed
Coulombe, P.A. & Fuchs, E. (1994). Molecular mechanisms of keratin gene disorders and other bullous diseases of the skin. In Molecular Mechanisms of Epithelial Cell Junctions: From Development to Disease, Citi, S. (Ed.), pp. 259–285. Austin, TX: RG Landes Co.Google Scholar
Cowin, P. & Burke, B. (1996). Cytoskeleton-membrane interactions. Curr Opin Cell Biol 8, 56–65.CrossRefGoogle ScholarPubMed
den Haan, A.D., Tan, B.Y., Zikusoka, M.N., Lladó, L.I., Jain, R., Daly, A., Tichnell, C., James, C., Amat-Alarcon, N., Abraham, T., Russell, S.D., Bluemke, D.A., Calkins, H., Dalal, D. & Judge, D.P. (2009). Comprehensive desmosome mutation analysis in North Americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation: Cardio Genetics 2, 428–435.Google ScholarPubMed
Farquhar, M.G. & Palade, G.E. (1963). Junctional complexes in various epithelia. J Cell Biol 17, 375–412.CrossRefGoogle ScholarPubMed
Fuchs, E. (1994). Intermediate filaments and disease: Mutations that cripple cell strength. J Cell Biol 125, 511–516.CrossRefGoogle ScholarPubMed
Gallicano, G.I., Bauer, C. & Fuchs, E. (2001). Rescuing desmoplakin function in extraembryonic ectoderm reveals an importance for desmoplakin in embryonic heart, neurepithelium, skin, and vasculature. Development 128, 929–941.CrossRefGoogle Scholar
Gallicano, G.I., Kouklis, P., Bauer, C., Yin, M., Vasioukhin, V., Degenstein, L. & Fuchs, E. (1998). Desmoplakin is required early in development for assembly of desmosomes and cytoskeletal linkage. J Cell Biol 143, 2009–2022.CrossRefGoogle ScholarPubMed
Garcia-Gras, E., Lombardi, R., Giocondo, M.J., Willerson, J.T., Schneider, M.D., Khoury, D.S. & Marian, A.J. (2006). Suppression of canonical Wnt/b-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy. J Clin Invest 116, 21012–21021.CrossRefGoogle Scholar
Garrod, D. (1993). Desmosomes and hemidesmosomes. Curr Opin Cell Biol 5, 30–40.CrossRefGoogle ScholarPubMed
Garrod, D.R. & Collins, J.E. (1994). Molecular biology of desmosomes and hemidesmosomes. In Molecular Mechanisms of Epithelial Cell Junctions: From Development to Disease, Citi, S. (Ed.), pp. 19–33. Austin, TX: RG Landes Co.Google Scholar
Hames, K.Y., Asimaki, A., Habib, N. & Saffitz, J.E. (2008). Cardiac-specific deletion of desmoplakin causes dilated cardiomyopathy and remodeling of gap junctions. Circulation 118, S284.Google Scholar
McLean, W.H.I. & Lane, E.B. (1995). Intermediate filaments in disease. Curr Opin Cell Biol 7, 118–125.CrossRefGoogle ScholarPubMed
Nakagawa, M., Price, R.L., Chintanawonges, C., Simpson, D.G., Horacek, M.J., Borg, T.K. & Terracio, L. (1997). Analysis of heart development in cultured rat embryos. J Mol Cell Cardiol 29, 369–379.CrossRefGoogle ScholarPubMed
Norgett, E.E., Hatsell, S.J., Carvajal-Huerta, L., Cabezas, J.C.R., Common, J., Purkis, P.E., Whittock, N., Leigh, I.M., Stevens, H.P. & Kelsell, D.P. (2000). Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Human Mol Genetics 9, 2761–2766.CrossRefGoogle ScholarPubMed
Norman, M., Simpson, M., Mogensen, J., Shaw, A., Hughes, S., Syrris, P., Sen-Chowdhry, S., Rowland, E., Crosby, A. & McKenna, W.J. (2005). Novel mutation in desmoplakin causes arrhythmogenic left ventricular cardiomyopathy. Circulation 112, 636–642.CrossRefGoogle ScholarPubMed
O'Keefe, E.J., Erickson, H.P. & Bennett, V. (1989). Desmoplakin I and desmoplakin II. Purification and characterization. J Biol Chem 264, 8310–8318.CrossRefGoogle ScholarPubMed
Porter, K.E. & Turner, N.A. (2009). Cardiac fibroblasts: At the heart of myocardial remodeling. Pharmacol Ther 123, 255–278.CrossRefGoogle ScholarPubMed
Ruiz, P., Brinkmann, V., Ledermann, B., Behrend, M., Grund, C., Thalhammer, C., Vogel, F., Birchmeier, C., Gunthert, U., Franke, W.W. & Birchmeir, W. (1996). Targeted mutation of plakoglobin in mice reveals essential functions of desmosomes in the embryonic heart. J Cell Biol 135, 215–225.CrossRefGoogle ScholarPubMed
Schmelz, M. & Franke, W.W. (1993). Complexus adhaerentes, a new group of desmoplakin-containing junctions in endothelial cells: The syndesmos connecting retothelial cells of lymph nodes. Eur J Cell Biol 61, 274–289.Google ScholarPubMed
Schmelz, M., Moll, R., Kuhn, C. & Franke, W.W. (1994). Complexus adhaerentes, a new group of desmoplakin-containing junctions in endothelial cells: II. Different types of lymphatic vessels. Differentiation 57, 97–117.CrossRefGoogle ScholarPubMed
Sharp, W.W., Simpson, D.G., Borg, T.K., Samarel, A.M. & Terracia, L. (1997). Mechanical forces regulate focal adhesion and costamere assembly in cardiac myocytes. Am J Physiol 273, H546–H556.Google ScholarPubMed
Simpson, D.G., Terracio, L., Terracio, M., Price, R.L., Turner, D.C. & Borg, T.K. (1994). Modulation of cardiac myocyte phenotype in vitro by the composition and orientation of the extracellular matrix. J Cell Physiol 161, 89–105.CrossRefGoogle ScholarPubMed
Uzumcu, A., Norgett, E.E., Dindar, A., Uyguner, O., Nisli, K., Kayserili, H., Sahin, S.E., Dupont, E., Severs, N.J., Leigh, I.M., Yuksel-Apak, M., Kelsell, D.P. & Wollnik, B. (2006). Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in a Naxos-like syndrome. J Med Genet 43, 1–8.Google Scholar
Valiron, O., Chevrier, V., Usson, Y., Breviario, F., Job, D. & Dejana, E. (1996). Desmoplakin expression and organization at human umbilical vein endothelial cell-to-cell junctions. J Cell Sci 109, 2141–2149.CrossRefGoogle ScholarPubMed
Zhou, X., Stuart, A., Dettin, L.E., Rodriguez, G., Hoel, B. & Gallicano, G.I. (2004). Desmoplakin is required for microvascular tube formation in culture. J Cell Sci 117, 3129–3140.CrossRefGoogle ScholarPubMed
Supplementary material: PDF

Bowers Supplementary Material

Supplementary Figure 1. 1611 specifically stains fibroblasts in the heart. A–D: Confocal micrograph of murine left ventricle showing 1611 staining ~red! of cardiac fibroblasts, myocytes with phalloidin ~green!, and nuclei with DAPI ~blue!. E–H: Confocal micrograph of murine left ventricle showing vimentin staining ~red! of cardiac fibroblasts,myocytes with phalloidin ~green!, and nuclei with DAPI ~blue!. 1611 antibody and antivimentin antibody stain the same cell population in the heart. Scale bars are shown in individual panels.

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