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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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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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