Bamji Shernaz X, Rico Beatriz, Kimes Nikole, Reichardt Louis F
Neuroscience Program, Howard Hughes Medical Institute, and Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.
J Cell Biol. 2006 Jul 17;174(2):289-99. doi: 10.1083/jcb.200601087. Epub 2006 Jul 10.
Neurons of the vertebrate central nervous system have the capacity to modify synapse number, morphology, and efficacy in response to activity. Some of these functions can be attributed to activity-induced synthesis and secretion of the neurotrophin brain-derived neurotrophic factor (BDNF); however, the molecular mechanisms by which BDNF mediates these events are still not well understood. Using time-lapse confocal analysis, we show that BDNF mobilizes synaptic vesicles at existing synapses, resulting in small clusters of synaptic vesicles "splitting" away from synaptic sites. We demonstrate that BDNF's ability to mobilize synaptic vesicle clusters depends on the dissociation of cadherin-beta-catenin adhesion complexes that occurs after tyrosine phosphorylation of beta-catenin. Artificially maintaining cadherin-beta-catenin complexes in the presence of BDNF abolishes the BDNF-mediated enhancement of synaptic vesicle mobility, as well as the longer-term BDNF-mediated increase in synapse number. Together, this data demonstrates that the disruption of cadherin-beta-catenin complexes is an important molecular event through which BDNF increases synapse density in cultured hippocampal neurons.
脊椎动物中枢神经系统的神经元能够根据活动情况改变突触数量、形态和效能。其中一些功能可归因于活动诱导的神经营养因子脑源性神经营养因子（BDNF）的合成与分泌；然而，BDNF介导这些事件的分子机制仍未完全清楚。通过延时共聚焦分析，我们发现BDNF可促使现有突触处的突触小泡移动，导致一小簇突触小泡从突触位点“分离”出来。我们证明，BDNF促使突触小泡簇移动的能力取决于β-连环蛋白酪氨酸磷酸化后发生的钙黏蛋白-β-连环蛋白黏附复合体的解离。在BDNF存在的情况下人工维持钙黏蛋白-β-连环蛋白复合体，会消除BDNF介导的突触小泡移动增强以及BDNF介导的突触数量的长期增加。总之，这些数据表明，钙黏蛋白-β-连环蛋白复合体的破坏是BDNF增加培养的海马神经元突触密度的一个重要分子事件。
