title: SNAREs Controlling Vesicular Release of BDNF and Development of Callosal Axons.
abstract: At presynaptic active zones, exocytosis of neurotransmitter vesicles (SVs) is driven by SNARE complexes that recruit Syb2 and SNAP25. However, it remains unknown which SNAREs promote the secretion of neuronal proteins, including those essential for circuit development and experience-dependent plasticity. Here we demonstrate that Syb2 and SNAP25 mediate the vesicular release of BDNF in axons and dendrites of cortical neurons, suggesting these SNAREs act in multiple spatially segregated secretory pathways. Remarkably, axonal secretion of BDNF is also strongly regulated by SNAP47, which interacts with SNAP25 but appears to be dispensable for exocytosis of SVs. Cell-autonomous ablation of SNAP47 disrupts the layer-specific branching of callosal axons of projection cortical neurons in vivo, and this phenotype is recapitulated by ablation of BDNF or its receptor, TrkB. Our results provide insights into the molecular mechanisms of protein secretion, and they define the functions of SNAREs in BDNF signaling and regulation of neuronal connectivity.
authors.affiliation: Department of Molecular and Cellular Neuroscience, The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA; The Dorris Neuroscience Center (DNC), The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Shimojo
authors.affiliation: Department of Molecular and Cellular Neuroscience, The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA; The Dorris Neuroscience Center (DNC), The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA.
authors.forename: Julien
authors.initials: J
authors.lastname: Courchet
authors.affiliation: Department of Molecular and Cellular Neuroscience, The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA; The Dorris Neuroscience Center (DNC), The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Pieraut
authors.affiliation: Department of Molecular and Cellular Neuroscience, The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA; The Dorris Neuroscience Center (DNC), The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Torabi-Rander
authors.affiliation: Department of Molecular and Cellular Neuroscience, The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA; The Dorris Neuroscience Center (DNC), The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA; The Kellogg School of Science and Technology, The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Sando
authors.affiliation: Department of Molecular and Cellular Neuroscience, The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA; The Dorris Neuroscience Center (DNC), The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA.
authors.forename: Franck
authors.initials: F
authors.lastname: Polleux
authors.affiliation: Department of Molecular and Cellular Neuroscience, The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA; The Dorris Neuroscience Center (DNC), The Scripps Research Institute (TSRI), La Jolla, CA 92037, USA. Electronic address: amaximov@scripps.edu.
authors.forename: Anton
authors.initials: A
authors.lastname: Maximov
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D005089:Exocytosis / Q000502:physiology*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D050766:Qb-SNARE Proteins / Q000378:metabolism; D050767:Qc-SNARE Proteins / Q000378:metabolism; D050600:SNARE Proteins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism*; D014162:Transfection; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D050600:SNARE Proteins; C494209:Snap25 protein, mouse; C512318:Snap47 protein, mouse; D050825:Synaptosomal-Associated Protein 25; D050988:Vesicle-Associated Membrane Protein 2; C494808:vesicle-associated membrane protein 2, mouse