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The tight junction protein CAR regulates cardiac conduction and cell-cell communication

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Item Type:Article
Title:The tight junction protein CAR regulates cardiac conduction and cell-cell communication
Creators Name:Lisewski, U., Shi, Y., Wrackmeyer, U., Fischer, R., Chen, C., Schirdewan, A., Juettner, R., Rathjen, F.G., Poller, W., Radke, M.H. and Gotthardt, M.
Abstract:The Coxsackievirus-adenovirus receptor (CAR) is known for its role in virus uptake and as a protein of the tight junction. It is predominantly expressed in the developing brain and heart and reinduced upon cardiac remodeling in heart disease. So far, the physiological functions of CAR in the adult heart are largely unknown. We have generated a heart-specific inducible CAR knockout (KO) and found impaired electrical conduction between atrium and ventricle that increased with progressive loss of CAR. The underlying mechanism relates to the cross talk of tight and gap junctions with altered expression and localization of connexins that affect communication between CAR KO cardiomyocytes. Our results indicate that CAR is not only relevant for virus uptake and cardiac remodeling but also has a previously unknown function in the propagation of excitation from the atrium to the ventricle that could explain the association of arrhythmia and Coxsackievirus infection of the heart.
Keywords:Atrioventricular Node, Cadherins, Cell Communication, Cultured Cells, Connexin 43, Coxsackievirus Infections, Electrocardiography, Electrophysiology, Gap Junctions, Heart, Heart Conduction System, Cardiac Myocytes, Phenotype, Virus Receptors, Tight Junctions, Animals, Mice
Source:Journal of Experimental Medicine
Publisher:Rockefeller University Press
Page Range:2369-2379
Date:29 September 2008
Additional Information:Copyright (c) 2008 by The Rockefeller University Press
Official Publication:https://doi.org/10.1084/jem.20080897
PubMed:View item in PubMed

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