The Solomon H. Snyder Department of Neuroscience and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Neuron. 2010 Aug 12;67(3):422-34. doi: 10.1016/j.neuron.2010.07.018.
We report a role for long-distance retrograde neurotrophin signaling in the establishment of synapses in the sympathetic nervous system. Target-derived NGF is both necessary and sufficient for formation of postsynaptic specializations on dendrites of sympathetic neurons. This, in turn, is a prerequisite for formation of presynaptic specializations, but not preganglionic axonal ingrowth from the spinal cord into sympathetic ganglia. We also find that NGF-TrkA signaling endosomes travel from distal axons to cell bodies and dendrites where they promote PSD clustering. Furthermore, the p75 neurotrophin receptor restricts PSD formation, suggesting an important role for antagonistic NGF-TrkA and p75 signaling pathways during retrograde control of synapse establishment. Thus, in addition to defining the appropriate number of sympathetic neurons that survive the period of developmental cell death, target-derived NGF also exerts control over the degree of connectivity between the spinal cord and sympathetic ganglia through retrograde control of synapse assembly.
我们报告了长距离逆行神经递素质信号在交感神经系统中突触形成中的作用。靶源性 NGF 对于交感神经元树突上的突触后特化的形成是必需和充分的。这反过来又是形成突触前特化的前提条件，但不是来自脊髓的节前轴突进入交感神经节。我们还发现，NGF-TrkA 信号转导内体从远端轴突迁移到细胞体和树突，在那里促进 PSD 聚集。此外，p75 神经营养因子受体限制 PSD 的形成，这表明在逆行控制突触形成过程中，NGF-TrkA 和 p75 信号通路具有拮抗作用。因此，除了确定在发育性细胞死亡期间存活的适当数量的交感神经元外，靶源性 NGF 还通过逆行控制突触组装来对脊髓和交感神经节之间的连接程度施加控制。
