Published online
doi:10.1084/jem.20080897
The Journal of Experimental Medicine, Vol. 205, No. 10, 2369-2379
The Rockefeller University Press, 0022-1007 $30.00
© Lisewski et al.
The tight junction protein CAR regulates cardiac conduction and cell–cell communication
Ulrike Lisewski1,
Yu Shi1,
Uta Wrackmeyer1,
Robert Fischer3,
Chen Chen1,
Alexander Schirdewan3,4,
Rene Jüttner2,
Fritz Rathjen2,
Wolfgang Poller4,
Michael H. Radke1, and
Michael Gotthardt1,5
1 Neuromuscular and Cardiovascular Cell Biology, 2 Developmental Neurobiology, Max Delbrück Center for Molecular Medicine (MDC), 13122 Berlin-Buch, Germany
3 HELIOS Kliniken GmbH, Franz-Volhard Klinik, Charité, Humboldt University, 13125 Berlin, Germany
4 Department of Cardiology, Campus Benjamin Franklin, D-12200 Berlin, Germany
5 Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, WA 99164
CORRESPONDENCE Michael Gotthardt: gotthardt{at}mdc-berlin.de
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.
Abbreviations used: AV, atrioventricular; CAR, Coxsackievirus-adenovirus receptor; E, embryonic day; ECG, electrocardiogram; EP, electrophysiology; HV, His-ventricle; MHC, myosin heavy chain.
U.L. and Y.S. contributed equally to this paper.
© 2008 Lisewski et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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