At the heart of inter- and intracellular signaling: the intercalated disc
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Proper cardiac function requires the synchronous mechanical and electrical coupling of individual cardiomyocytes. The intercalated disc (ID) mediates coupling of neighboring myocytes through intercellular signaling. Intercellular communication is highly regulated via intracellular signaling, and signaling pathways originating from the ID control cardiomyocyte remodeling and function. Herein, we present an overview of the inter- and intracellular signaling that occurs at and originates from the intercalated disc in normal physiology and pathophysiology. This review highlights the importance of the intercalated disc as an integrator of signaling events regulating homeostasis and stress responses in the heart and the center of several pathophysiological processes mediating the development of cardiomyopathies.
KeywordsIntercalated disc Intercalated disc Heart Cardiomyocyte Cardiomyopathy
The authors acknowledge funding from the National Institutes of Health (HL121284 and HL136951 to F.A. and HL116778 to M.A.A.) and a grant from the Saving tiny Hearts Society (M.A.A).
Compliance with ethical standards
Conflict of interest
Heather R. Manring declares that she has no conflicts of interest. Lisa E. Dorn declares that she has no conflicts of interest. Aidan Ex-Willey declares that he has no conflicts of interest. Federica Accornero declares that she has no conflicts of interest. Maegen A. Ackermann declares that she has no conflicts of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- Baurand A et al (2007) Beta-catenin downregulation is required for adaptive cardiac remodeling. Circ Res 100:1353–1362. https://doi.org/10.1161/01.RES.0000266605.63681.5a PubMedCrossRefGoogle Scholar
- Borrmann CM, Grund C, Kuhn C, Hofmann I, Pieperhoff S, Franke WW (2006) The area composita of adhering junctions connecting heart muscle cells of vertebrates. II. Colocalizations of desmosomal and fascia adhaerens molecules in the intercalated disk. Eur J Cell Biol 85:469–485. https://doi.org/10.1016/j.ejcb.2006.02.009 PubMedCrossRefGoogle Scholar
- Dowling JJ, Gibbs E, Russell M, Goldman D, Minarcik J, Golden JA, Feldman EL (2008) Kindlin-2 is an essential component of intercalated discs and is required for vertebrate cardiac structure and function. Circ Res 102:423–431. https://doi.org/10.1161/CIRCRESAHA.107.161489 PubMedCrossRefGoogle Scholar
- Franke WW, Borrmann CM, Grund C, Pieperhoff S (2006) The area composita of adhering junctions connecting heart muscle cells of vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by immunoelectron microscopy of desmosomal proteins. Eur J Cell Biol 85:69–82. https://doi.org/10.1016/j.ejcb.2005.11.003 PubMedCrossRefGoogle Scholar
- Franke WW et al (2007) The area composita of adhering junctions connecting heart muscle cells of vertebrates—III: assembly and disintegration of intercalated disks in rat cardiomyocytes growing in culture. Eur J Cell Biol 86:127–142. https://doi.org/10.1016/j.ejcb.2006.11.003 PubMedCrossRefGoogle Scholar
- Lombardi R, da Graca Cabreira-Hansen M, Bell A, Fromm RR, Willerson JT, Marian AJ (2011) Nuclear plakoglobin is essential for differentiation of cardiac progenitor cells to adipocytes in arrhythmogenic right ventricular cardiomyopathy. Circ Res 109:1342–1353. https://doi.org/10.1161/CIRCRESAHA.111.255075 PubMedPubMedCentralCrossRefGoogle Scholar
- Mohler PJ, Rivolta I, Napolitano C, LeMaillet G, Lambert S, Priori SG, Bennett V (2004) Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes. Proc Natl Acad Sci U S A 101:17533–17538. https://doi.org/10.1073/pnas.0403711101 PubMedPubMedCentralCrossRefGoogle Scholar
- Pieperhoff S, Franke WW (2007) The area composita of adhering junctions connecting heart muscle cells of vertebrates—IV: coalescence and amalgamation of desmosomal and adhaerens junction components—late processes in mammalian heart development. Eur J Cell Biol 86:377–391. https://doi.org/10.1016/j.ejcb.2007.04.001 PubMedCrossRefGoogle Scholar
- \Satomi-Kobayashi S et al (2009) Deficiency of nectin-2 leads to cardiac fibrosis and dysfunction under chronic pressure overload. Hypertension 54:825–831. https://doi.org/10.1161/HYPERTENSIONAHA.109.130443 PubMedCrossRefGoogle Scholar
- van Bemmelen MX et al (2004) Cardiac voltage-gated sodium channel Nav1.5 is regulated by Nedd4-2 mediated ubiquitination. Circ Res 95:284–291. https://doi.org/10.1161/01.RES.0000136816.05109.89 PubMedCrossRefGoogle Scholar
- Wang N et al (2016) Activation of Wnt/beta-catenin signaling by hydrogen peroxide transcriptionally inhibits NaV1.5 expression. Free Radic Biol Med 96:34–44. https://doi.org/10.1016/j.freeradbiomed.2016.04.003 PubMedPubMedCentralCrossRefGoogle Scholar