Badal Kerriann K, Zhao Yibo, Raveendra Bindu L, Lozano-Villada Sebastian, Miller Kyle E, Puthanveettil Sathyanarayanan V
Department of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, 130 Scripps Way, Jupiter, FL 33458, USA.
Integrative Biology PhD Program, Charles E. Schmidt College of Science, Florida Atlantic University, Jupiter, FL 33458, USA.
bioRxiv. 2024 Jun 29:2024.06.28.601272. doi: 10.1101/2024.06.28.601272.
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 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.
细胞器的双向长距离运输对于细胞体与突触之间的通讯至关重要。然而，这种运输如何被调节以实现突触形成、维持和可塑性的机制尚未完全明确。在此，我们通过定量分析表明，在鳃-虹吸管退缩反射中维持感觉神经元-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，虽然在突触形成后12小时内顺行方向的线粒体运输增加，但溶酶体囊泡逆行运输的减少在突触形成三天后才出现。此外，我们发现由神经调节性神经递质5-羟色胺诱导的学习过程中形成新突触会在24小时内进一步减少溶酶体囊泡运输，而在暴露后一小时内顺行方向的线粒体运输增加。对几种信号通路的药理学抑制确定蛋白激酶A（PKA）是突触维持期间溶酶体囊泡逆行运输的关键调节因子。这些结果表明，突触形成会导致长距离运输中细胞器特异性和方向特异性的持久变化，为突触维持和可塑性的潜在机制提供了见解。
