biostudies-literatureWrackmeyer UDeutsche Forschungsgemeinschaft6768https://www.ebi.ac.uk/biostudies/studies/S-EPMC6494904biostudies-literatureUnknown9(1)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 Scientific reportsThe cell adhesion protein CAR is a negative regulator of synaptic transmission.PMC6494904DFG Ra424/5-1Postdoc FellowshipSFB-TR/19SFB 665Kaldrack JPannasch UGimber NSchmitz DJuttner RPurfurst BRathjen FGHaucke VGotthardt MFreiberg FWrackmeyer UKainmueller DfalseThe cell adhesion protein CAR is a negative regulator of synaptic transmission.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 2019-01-01T00:00:00Z2019 May2026-05-07T03:45:28.784Z2019-06-06T23:26:13ZS-EPMC64949043104366310.1038/s41598-019-43150-5