Department of Pharmacology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
J Pharmacol Sci. 2019 Oct;141(2):91-96. doi: 10.1016/j.jphs.2019.10.001. Epub 2019 Oct 17.
Neurons extend axons far from cell bodies, and retrograde communications from distal axons to cell bodies and/or dendrites play critical roles in the development and maintenance of neuronal circuits. In neurotrophin signaling, the retrograde axonal transport of endosomes containing active ligand-receptor complexes from distal axons to somatodendrite compartments mediates retrograde signaling. However, the generality and specificity of these endosome-based transportations called "signaling endosomes" remain to be elucidated. Here, I summarize the discovery of semaphorin3A signaling endosomes, the first example other than neurotrophins to regulate dendritic development via AMPA receptor GluA2 localization in dendrites. The molecular components of Sema3A and neurotrophin signaling endosomes are distinct, but partially overlap to regulate specific and common cellular events. Because receptors are transported back to the cell bodies, neurons must replenish receptors on the growth cone surface to ensure continued response to the target-derived ligands. Recent findings have demonstrated that retrograde signaling endosomes also induce anterograde delivery of nascent receptors in neurotrophin signaling. The coupling between anterograde and retrograde axonal transport via signaling endosomes therefore plays a critical role in regulating proper neuronal network formation.
神经元从细胞体延伸出轴突，从远端轴突到细胞体和/或树突的逆行通讯在神经元回路的发育和维持中起着关键作用。在神经营养因子信号转导中，含有活性配体-受体复合物的内体从远端轴突逆行运输到胞体树突区室，介导逆行信号转导。然而，这些基于内体的运输（称为“信号内体”）的普遍性和特异性仍有待阐明。在这里，我总结了 Sema3A 信号内体的发现，这是第一个除神经营养因子以外的例子，通过 AMPA 受体 GluA2 在树突中的定位来调节树突发育。Sema3A 和神经营养因子信号内体的分子成分不同，但部分重叠，以调节特定和共同的细胞事件。由于受体被运回到细胞体，神经元必须在生长锥表面补充受体，以确保对靶源性配体的持续反应。最近的研究结果表明，逆行信号内体也诱导神经营养因子信号中新生受体的正向运输。因此，通过信号内体的顺行和逆行轴突运输的偶联在调节适当的神经元网络形成中起着关键作用。
