Scribble interacts with beta-catenin to localize synaptic vesicles to synapses.

An understanding of how synaptic vesicles are recruited to and maintained at presynaptic compartments is required to discern the molecular mechanisms underlying presynaptic assembly and plasticity. We have previously demonstrated that cadherin-beta-catenin complexes cluster synaptic vesicles at presynaptic sites. Here we show that scribble interacts with the cadherin-beta-catenin complex to coordinate vesicle localization. Scribble and beta-catenin are colocalized at synapses and can be coimmunoprecipitated from neuronal lysates, indicating an interaction between scribble and beta-catenin at the synapse. Using an RNA interference approach, we demonstrate that scribble is important for the clustering of synaptic vesicles at synapses. Indeed, in scribble knockdown cells, there is a diffuse distribution of synaptic vesicles along the axon, and a deficit in vesicle recycling. Despite this, synapse number and the distribution of the presynaptic active zone protein, bassoon, remain unchanged. These effects largely phenocopy those observed after ablation of beta-catenin. In addition, we show that loss of beta-catenin disrupts scribble localization in primary neurons but that the localization of beta-catenin is not dependent on scribble. Our data supports a model by which scribble functions downstream of beta-catenin to cluster synaptic vesicles at developing synapses.