UCLA

Ubiquitination of a target protein is an important post-translational modification. There is evidence for the involvement of ubiquitination of presynaptic proteins in synaptic transmission. Vesicle associated membrane protein (VAMP2) is a presynaptic protein that is fundamental for vesicle docking and fusion and here we test the hypothesis that ubiquitination of VAMP2 is important for synaptic transmission. To test this hypothesis, we downregulated expression of endogenous VAMP2 and allowed for the expression of mutant VAMP2 that cannot undergo ubiquitination. Using electrophysiological recordings in cortical neuronal cultures from autapses (synapses made by a neuron onto itself), we found that knocking down endogenous VAMP2 reduces synaptic transmission and this is rescued with exogenous VAMP2. Our findings indicate that E1 inhibition alters synaptic transmission in control neurons, but not in neurons rescued with mutant VAMP2 with a knock down background. Our findings support our hypothesis that ubiquitination of VAMP2 modulates synaptic transmission.