PDF(Pubmed)
Abstract：
The bidirectional long-distance transport of organelles is crucial for cell body-synapse communication. However, the mechanisms by which this transport is modulated for synapse formation, maintenance, and plasticity are not fully understood. Here, we demonstrate through quantitative analyses that maintaining sensory neuron-motor neuron synapses in the Aplysia gill-siphon withdrawal reflex is linked to a sustained reduction in the retrograde transport of lysosomal vesicles in sensory neurons. Interestingly, while mitochondrial transport in the anterograde direction increases within 12 hours of synapse formation, the reduction in lysosomal vesicle retrograde transport appears three days after synapse formation. Moreover, we find that formation of new synapses during learning induced by neuromodulatory neurotransmitter serotonin further reduces lysosomal vesicle transport within 24 hours, whereas mitochondrial transport increases in the anterograde direction within one hour of exposure. Pharmacological inhibition of several signaling pathways pinpoints PKA as a key regulator of retrograde transport of lysosomal vesicles during synapse maintenance. These results demonstrate that synapse formation leads to organelle-specific and direction specific enduring changes in long-distance transport, offering insights into the mechanisms underlying synapse maintenance and plasticity.
摘要：
细胞器的双向长距离运输对于细胞体-突触通信至关重要。然而,调节这种运输以形成突触的机制，维护,和可塑性还没有完全理解。这里,我们通过定量分析证明，维持Aplysiag-虹吸戒断反射中的感觉神经元-运动神经元突触与感觉神经元中溶酶体囊泡逆行运输的持续减少有关。有趣的是,而线粒体顺行方向的转运在突触形成的12小时内增加，溶酶体囊泡逆行转运减少出现在突触形成后3天。此外，我们发现神经调节神经递质5-羟色胺诱导的学习过程中新突触的形成在24小时内进一步减少了溶酶体囊泡的运输，而线粒体转运在暴露后一小时内沿顺行方向增加。几种信号通路的药理学抑制指出PKA是突触维持期间溶酶体囊泡逆行转运的关键调节因子。这些结果表明，突触形成导致了细胞器特异性和方向特异性的长距离运输的持久变化，提供对突触维持和可塑性的潜在机制的见解。
