The tight junction protein CAR regulates cardiac conduction and cell-cell communication.
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.
Lisewski
Ulrike
U
Neuromuscular and Cardiovascular Cell Biology, Max Delbrück Center for Molecular Medicine (MDC), 13122 Berlin-Buch, Germany.
Shi
Yu
Y
Wrackmeyer
Uta
U
Fischer
Robert
R
Chen
Chen
C
Schirdewan
Alexander
A
Jüttner
Rene
R
Rathjen
Fritz
F
Poller
Wolfgang
W
Radke
Michael H
MH
Gotthardt
Michael
M
D000818:Animals; D001283:Atrioventricular Node / Q000502:physiology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D003384:Coxsackievirus Infections / Q000378:metabolism / Q000503:physiopathology; D004562:Electrocardiography; D004594:Electrophysiology; D017629:Gap Junctions / Q000378:metabolism; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D006329:Heart Conduction System / Q000033:anatomy & histology / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism*
C568771:CLMP protein, human; C568772:CLMP protein, mouse; D015820:Cadherins; D018031:Connexin 43; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus
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