Section on Neural Development and Plasticity, National Institute of Child Health and Human Development, Bethesda, MD 20892-3714, USA.
Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):15924-9. doi: 10.1073/pnas.1207767109. Epub 2012 Sep 10.
Formation of specific neuronal connections often involves competition between adjacent axons, leading to stabilization of the active terminal, while retraction of the less active ones. The underlying molecular mechanisms remain unknown. We show that activity-dependent conversion of pro-brain-derived neurotrophic factor (proBDNF) to mature (m)BDNF mediates synaptic competition. Stimulation of motoneurons triggers proteolytic conversion of proBDNF to mBDNF at nerve terminals. In Xenopus nerve-muscle cocultures, in which two motoneurons innervate one myocyte, proBDNF-p75(NTR) signaling promotes retraction of the less active terminal, whereas mBDNF-tyrosine-related kinase B (TrkB) p75NTR (p75 neurotrophin receptor) facilitates stabilization of the active one. Thus, proBDNF and mBDNF may serve as potential "punishment" and "reward" signals for inactive and active terminals, respectively, and activity-dependent conversion of proBDNF to mBDNF may regulate synapse elimination.
特定神经元连接的形成通常涉及相邻轴突之间的竞争，导致活跃终末的稳定，而不活跃的终末则回缩。其潜在的分子机制尚不清楚。我们发现，活性依赖性的前脑源性神经营养因子（proBDNF）向成熟（m）BDNF 的转化介导了突触竞争。运动神经元的刺激会在神经末梢触发 proBDNF 向 mBDNF 的蛋白水解转化。在爪蟾的神经-肌肉共培养物中，两个运动神经元支配一个肌细胞，proBDNF-p75（NTR）信号促进不活跃终末的回缩，而 mBDNF-酪氨酸相关激酶 B（TrkB）p75NTR（p75 神经营养因子受体）则有利于活跃终末的稳定。因此，proBDNF 和 mBDNF 可能分别作为无活性和活性终末的潜在“惩罚”和“奖励”信号，而 proBDNF 向 mBDNF 的活性依赖性转化可能调节突触消除。
