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The cell adhesion protein CAR is a negative regulator of synaptic transmission

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Item Type:Article
Title:The cell adhesion protein CAR is a negative regulator of synaptic transmission
Creators Name:Wrackmeyer, U. and Kaldrack, J. and Jüttner, R. and Pannasch, U. and Gimber, N. and Freiberg, F. and Purfürst, B. and Kainmueller, D. and Schmitz, D. and Haucke, V. and Rathjen, F.G. and Gotthardt, M.
Abstract:The Coxsackievirus and adenovirus receptor (CAR) is essential for normal electrical conductance in the heart, but its role in the postnatal brain is largely unknown. Using brain specific CAR knockout mice (KO), we discovered an unexpected role of CAR in neuronal communication. This includes increased basic synaptic transmission at hippocampal Schaffer collaterals, resistance to fatigue, and enhanced long-term potentiation. Spontaneous neurotransmitter release and speed of endocytosis are increased in KOs, accompanied by increased expression of the exocytosis associated calcium sensor synaptotagmin 2. Using proximity proteomics and binding studies, we link CAR to the exocytosis machinery as it associates with syntenin and synaptobrevin/VAMP2 at the synapse. Increased synaptic function does not cause adverse effects in KO mice, as behavior and learning are unaffected. Thus, unlike the connexin-dependent suppression of atrioventricular conduction in the cardiac knockout, communication in the CAR deficient brain is improved, suggesting a role for CAR in presynaptic processes.
Keywords:Animal Behavior, Brain, Cell Adhesion, Coxsackie and Adenovirus Receptor-Like Membrane Protein, Exocytosis, Knockout Mice, Long-Term Potentiation, Neurons, Synapses, Synaptic Transmission, Synaptic Vesicles, Animals, Mice
Source:Scientific Reports
Publisher:Nature Publishing Group
Page Range:6768
Date:1 May 2019
Official Publication:https://doi.org/10.1038/s41598-019-43150-5
PubMed:View item in PubMed

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