β-Pix Modulates Actin-Mediated Recruitment of Synaptic Vesicles to Synapses

Presynaptic compartments are formed through the recruitment of preassembled clusters of proteins to points of cell-cell contact, however, the molecular mechanism(s) underlying this process remains unclear. We demonstrate that clusters of polymerized actin can recruit and maintain synaptic vesicles to discrete sites along the axon, and that cadherin/beta-catenin/scribble/beta-pix complexes play an important role in this event. Previous work has demonstrated that beta-catenin and scribble are important for the clustering of vesicles at synapses. We demonstrate that beta-pix, a Rac/Cdc42 guanine nucleotide exchange factor (GEF), forms a complex with cadherin, beta-catenin, and scribble at synapses and enhances localized actin polymerization in rat hippocampal neurons. In cells expressing beta-pix siRNA or dominant-negative beta-pix that lacks its GEF activity, actin polymerization at synapses is dramatically reduced, and synaptic vesicle localization is disrupted. This beta-pix phenotype can be rescued by cortactin overexpression, suggesting that beta-pix-mediated actin polymerization at synapses regulates vesicle localization.