The vSNAREs VAMP2 and VAMP4 control recycling and intracellular sorting of post-synaptic receptors in neuronal dendrites

Cell Reports (2021)

May Bakr, Damien Jullié, Julia Krapivkina, Vincent Paget-Blanc, Lou Bouit, Jennifer Petersen, Natacha Retailleau, Christelle Breillat, Etienne Herzog, Daniel Choquet, David Perrais

The endosomal recycling system dynamically tunes synaptic strength which underlies synaptic plasticity. Exocytosis is involved in the expression of long term potentiation (LTP), as postsynaptic cleavage of the SNARE protein VAMP2 by tetanus toxin blocks LTP. Moreover, induction of LTP increases the exocytosis of transferrin receptors (TfR), markers of recycling endosomes (REs), as well as post-synaptic AMPA type receptors. However, the interplay between AMPAR and TfR exocytosis remains unclear. Here we identify VAMP4 as the vesicular SNARE that mediates most dendritic RE exocytosis. In contrast, VAMP2 plays a minor role in RE exocytosis. LTP induction increases the exocytosis of both VAMP2 and VAMP4 labelled organelles. Knock-down (KD) of VAMP4 decreases TfR recycling but increases AMPAR recycling. Moreover, VAMP4 KD increases AMPAR-mediated synaptic transmission, which consequently occludes LTP expression. The opposing changes in AMPAR and TfR recycling upon VAMP4 KD reveal their sorting into separate endosomal populations.