title: β-Pix modulates actin-mediated recruitment of synaptic vesicles to synapses.
abstract: 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/β-catenin/scribble/β-pix complexes play an important role in this event. Previous work has demonstrated that β-catenin and scribble are important for the clustering of vesicles at synapses. We demonstrate that β-pix, a Rac/Cdc42 guanine nucleotide exchange factor (GEF), forms a complex with cadherin, β-catenin, and scribble at synapses and enhances localized actin polymerization in rat hippocampal neurons. In cells expressing β-pix siRNA or dominant-negative β-pix that lacks its GEF activity, actin polymerization at synapses is dramatically reduced, and synaptic vesicle localization is disrupted. This β-pix phenotype can be rescued by cortactin overexpression, suggesting that β-pix-mediated actin polymerization at synapses regulates vesicle localization.
authors: Department of Cellular and Physiological Sciences and the Brain Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors: Yu
authors: Y
authors: Sun
authors: Shernaz X
authors: SX
authors: Bamji
mesh_terms: D000199:Actins / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000502:physiology*; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D064067:Rho Guanine Nucleotide Exchange Factors; D013569:Synapses / Q000737:chemistry / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000737:chemistry / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism; D051176:beta Catenin / Q000737:chemistry / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; C548802:scribble protein, rat