Shakiryanova Dinara, Tully Arvonn, Levitan Edwin S
Department of Pharmacology, University of Pittburgh, Pittsburgh, Pennsylvania 15261, USA.
Nat Neurosci. 2006 Jul;9(7):896-900. doi: 10.1038/nn1719. Epub 2006 Jun 11.
Synapses require resources synthesized in the neuronal soma, but there are no known mechanisms to overcome delays associated with the synthesis and axonal transport of new proteins generated in response to activity, or to direct resources specifically to active synapses. Here, in vivo imaging of the Drosophila melanogaster neuromuscular junction reveals a cell-biological strategy that addresses these constraints. Peptidergic vesicles continually transit through resting terminals, but retrograde peptidergic vesicle flux is accessed following activity to rapidly boost neuropeptide content in synaptic boutons. The presence of excess transiting vesicles implies that synaptic neuropeptide stores are limited by the capture of peptidergic vesicles at the terminal, rather than by synthesis in the soma or delivery via the axon. Furthermore, activity-dependent capture from a pool of transiting vesicles provides a nerve terminal-based mechanism for directing distally and slowly generated resources quickly to active synapses. Finally, retrograde transport in the nerve terminal is regulated by activity.
突触需要在神经元胞体中合成的资源,但目前尚不清楚有哪些机制可以克服与响应活动而产生的新蛋白质的合成和轴突运输相关的延迟,或者将资源特异性地导向活跃的突触。在这里,对果蝇神经肌肉接头的体内成像揭示了一种应对这些限制的细胞生物学策略。肽能囊泡不断通过静息终末,但在活动后会利用逆行肽能囊泡通量来快速增加突触小体中的神经肽含量。存在过量的转运囊泡意味着突触神经肽储备受到终末对肽能囊泡的捕获限制,而不是受胞体合成或通过轴突运输的限制。此外,从转运囊泡池中进行的活动依赖性捕获提供了一种基于神经终末的机制,可将在远处缓慢产生的资源快速导向活跃的突触。最后,神经终末中的逆行运输受活动调节。