The Intercalated Disc: a Mechanosensing Signalling Node in Cardiomyopathy

Overview

Journal Biophys Rev

Publisher Springer

Specialty Biophysics

Date 2020 Jul 15

PMID 32661904

Citations 17

Authors

Mihai Pruna

Elisabeth Ehler

Affiliations

Soon will be listed here.

Abstract

Cardiomyocytes, the cells generating contractile force in the heart, are connected to each other through a highly specialised structure, the intercalated disc (ID), which ensures force transmission and transduction between neighbouring cells and allows the myocardium to function in synchrony. In addition, cardiomyocytes possess an intrinsic ability to sense mechanical changes and to regulate their own contractile output accordingly. To achieve this, some of the components responsible for force transmission have evolved to sense changes in tension and to trigger a biochemical response that results in molecular and cellular changes in cardiomyocytes. This becomes of particular importance in cardiomyopathies, where the heart is exposed to increased mechanical load and needs to adapt to sustain its contractile function. In this review, we will discuss key mechanosensing elements present at the intercalated disc and provide an overview of the signalling molecules involved in mediating the responses to changes in mechanical force.

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References

Han M, de Rooij J . Converging and Unique Mechanisms of Mechanotransduction at Adhesion Sites. Trends Cell Biol. 2016; 26(8):612-623. DOI: 10.1016/j.tcb.2016.03.005. View

Schaller M, Hildebrand J, Shannon J, Fox J, Vines R, Parsons J . Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src. Mol Cell Biol. 1994; 14(3):1680-8. PMC: 358526. DOI: 10.1128/mcb.14.3.1680-1688.1994. View

Carisey A, Ballestrem C . Vinculin, an adapter protein in control of cell adhesion signalling. Eur J Cell Biol. 2010; 90(2-3):157-63. PMC: 3526775. DOI: 10.1016/j.ejcb.2010.06.007. View

Lu S, Crawford G, Dore J, Anderson S, Despres D, Horowits R . Cardiac-specific NRAP overexpression causes right ventricular dysfunction in mice. Exp Cell Res. 2011; 317(8):1226-37. PMC: 3070810. DOI: 10.1016/j.yexcr.2011.01.020. View

Sit B, Gutmann D, Iskratsch T . Costameres, dense plaques and podosomes: the cell matrix adhesions in cardiovascular mechanosensing. J Muscle Res Cell Motil. 2019; 40(2):197-209. PMC: 6726830. DOI: 10.1007/s10974-019-09529-7. View

Fukuda R, Gunawan F, Ramadass R, Beisaw A, Konzer A, Mullapudi S . Mechanical Forces Regulate Cardiomyocyte Myofilament Maturation via the VCL-SSH1-CFL Axis. Dev Cell. 2019; 51(1):62-77.e5. DOI: 10.1016/j.devcel.2019.08.006. View

Bachelot C, Rameh L, Parsons T, Cantley L . Association of phosphatidylinositol 3-kinase, via the SH2 domains of p85, with focal adhesion kinase in polyoma middle t-transformed fibroblasts. Biochim Biophys Acta. 1996; 1311(1):45-52. DOI: 10.1016/0167-4889(95)00176-x. View

Schlaepfer D, Hanks S, Hunter T, van der Geer P . Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase. Nature. 1994; 372(6508):786-91. DOI: 10.1038/372786a0. View

Li M, Mruk D, Lee W, Cheng C . Connexin 43 and plakophilin-2 as a protein complex that regulates blood-testis barrier dynamics. Proc Natl Acad Sci U S A. 2009; 106(25):10213-8. PMC: 2700929. DOI: 10.1073/pnas.0901700106. View

10.

Senetar M, Moncman C, McCann R . Talin2 is induced during striated muscle differentiation and is targeted to stable adhesion complexes in mature muscle. Cell Motil Cytoskeleton. 2006; 64(3):157-73. DOI: 10.1002/cm.20173. View

11.

Lyon R, Zanella F, Omens J, Sheikh F . Mechanotransduction in cardiac hypertrophy and failure. Circ Res. 2015; 116(8):1462-1476. PMC: 4394185. DOI: 10.1161/CIRCRESAHA.116.304937. View

12.

Wu S, Budnar S, Yap A, Gomez G . Pulsatile contractility of actomyosin networks organizes the cellular cortex at lateral cadherin junctions. Eur J Cell Biol. 2014; 93(10-12):396-404. DOI: 10.1016/j.ejcb.2014.09.001. View

13.

Truszkowska G, Bilinska Z, Muchowicz A, Pollak A, Biernacka A, Kozar-Kaminska K . Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy. Sci Rep. 2017; 7(1):3362. PMC: 5469774. DOI: 10.1038/s41598-017-03189-8. View

14.

Furst D, Osborn M, Nave R, Weber K . The organization of titin filaments in the half-sarcomere revealed by monoclonal antibodies in immunoelectron microscopy: a map of ten nonrepetitive epitopes starting at the Z line extends close to the M line. J Cell Biol. 1988; 106(5):1563-72. PMC: 2115059. DOI: 10.1083/jcb.106.5.1563. View

15.

Pfister R, Acksteiner C, Baumgarth J, Burst V, Geissler H, Margulies K . Loss of beta1D-integrin function in human ischemic cardiomyopathy. Basic Res Cardiol. 2006; 102(3):257-64. DOI: 10.1007/s00395-006-0640-1. View

16.

Zemljic-Harpf A, Miller J, Henderson S, Wright A, Manso A, Elsherif L . Cardiac-myocyte-specific excision of the vinculin gene disrupts cellular junctions, causing sudden death or dilated cardiomyopathy. Mol Cell Biol. 2007; 27(21):7522-37. PMC: 2169049. DOI: 10.1128/MCB.00728-07. View

17.

Blaxall B, Spang R, Rockman H, Koch W . Differential myocardial gene expression in the development and rescue of murine heart failure. Physiol Genomics. 2003; 15(2):105-14. DOI: 10.1152/physiolgenomics.00087.2003. View

18.

Leerberg J, Gomez G, Verma S, Moussa E, Wu S, Priya R . Tension-sensitive actin assembly supports contractility at the epithelial zonula adherens. Curr Biol. 2014; 24(15):1689-99. PMC: 5103636. DOI: 10.1016/j.cub.2014.06.028. View

19.

Palaniyandi S, Sun L, Ferreira J, Mochly-Rosen D . Protein kinase C in heart failure: a therapeutic target?. Cardiovasc Res. 2009; 82(2):229-39. PMC: 2675930. DOI: 10.1093/cvr/cvp001. View

20.

Eigenthaler M, Engelhardt S, Schinke B, Kobsar A, Schmitteckert E, Gambaryan S . Disruption of cardiac Ena-VASP protein localization in intercalated disks causes dilated cardiomyopathy. Am J Physiol Heart Circ Physiol. 2003; 285(6):H2471-81. DOI: 10.1152/ajpheart.00362.2003. View