Role of the Coxsackievirus and Adenovirus Receptor CAR in Synaptic Transmission and Memory Formation

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The Coxsackievirus-adenovirus-receptor (CAR) is a transmembrane protein of the Immunoglobulin-superfamily (IgSF) and was initially identified as a virus receptor related to human myocarditis, pancreatitis and meningoencephalitis. CAR is predominantly expressed in the developing heart and brain, downregulated after birth, and re-induced in disease. Its function was primarily analyzed in the heart where it contributes to embryonic and adult remodeling. In addition, we have recently uncovered a novel role for CAR in electrical conduction from atrium to cardiac ventricle that relates to the interaction of CAR with gap-junction proteins and proposed a similar role of CAR in synaptic transmission. To test this hypothesis, we have generated brain specific CAR knockout mice and found that communication between neurons is facilitated in these animals. Our preliminary analysis suggests improved synaptic signal transmission and long-term potentiation in CAR KO mice. We will study these phenotypes on the molecular, cellular, and organ level to elucidate the role of CAR in neuronal transmission. Accordingly, we plan to analyze how car affects spatial and contextual learning, its role in exo- and endocytosis of synaptic vesicles, and its effect on localization and function of pre- and post-synaptic proteins.The brain specific CAR knockout presents with improved synaptic transmission, which should translate to enhanced cognitive function. Thus, the proposed molecular and functional analysis could establish CAR as a therapeutic target to improve memory formation in ageing and disease.