@misc{oai:repo.qst.go.jp:00065827, author = {Shimojyo, Masafumi and Courchet, Julien and Pieraut, Simon and Torabi-Rander, Nina and Sando, Richard and Polleux, Franck and Higuchi, Makoto and Maximov, Anton and 下條 雅文 and 樋口 真人}, month = {Jan}, note = {Neurons employ a diverse repertoire of trafficking organelles for secretion of soluble molecules and recycling of membrane components, and these mechanisms are essential for development and maintenance of brain environment. Recent studies have identified the core components of a secretory apparatus that triggers the release of neurotransmitters from presynaptic terminals. Synaptic vesicle exocytosis is mediated by SNARE proteins, Synaptobrevin/VAMP2 (Syb2), SNAP25 and Syntaxin1, whose assembly into ternary complexes facilitate membrane fusion. A variety of diffusible peptide cues also appear to be transported by vesicles and undergo exocytosis, supporting the hypothesis that diverse SNAREs independently control different type of membrane fusion. Among such peptide cues, the brain-derived neurotrophic factor (BDNF) is known to play many critical roles in the nervous system. However, the molecular mechanisms that control the secretion of BDNF and other diffusible protein cues remain largely unknown. Here, we demonstrate that, using total internal reflection fluorescence microscopy and BDNF fused to pH-sensitive GFP variant pHluorin, activity-dependent exocytosis of BDNF from somatodendrites and axons is mediated by SNARE proteins Syb2 and SNAP25, suggesting these SNAREs act in multiple secretory pathways. Importantly, axonal secretion of BDNF is also specifically regulated by SNAP47. Cell-autonomous shRNA mediated knockdown of SNAP47 impairs the targeting and terminal branching of callosal axons in vivo, similar to knockdown of BDNF and its receptor TrkB. Taken together, these novel SNARE functions in BDNF secretion provide an important insight for neuronal circuit connectivity during brain development and/or maintenance., 新学術領域 脳内環境 班会議 第2回 若手研究者シンポジウム}, title = {Neuronal secretory pathway essential for development and maintenance of brain circuit and synaptic function}, year = {2015} }