title: The tight junction protein CAR regulates cardiac conduction and cell-cell communication.
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.
authors.affiliation: Neuromuscular and Cardiovascular Cell Biology, Max Delbrück Center for Molecular Medicine (MDC), 13122 Berlin-Buch, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lisewski
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.forename: Uta
authors.initials: U
authors.lastname: Wrackmeyer
authors.forename: Robert
authors.initials: R
authors.lastname: Fischer
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Alexander
authors.initials: A
authors.lastname: Schirdewan
authors.forename: Rene
authors.initials: R
authors.lastname: Jüttner
authors.forename: Fritz
authors.initials: F
authors.lastname: Rathjen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Poller
authors.forename: Michael H
authors.initials: MH
authors.lastname: Radke
authors.forename: Michael
authors.initials: M
authors.lastname: Gotthardt
mesh_terms: 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*
chemical_list: 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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