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突触形成激活了一个转录程序,使线粒体在双向运输中具有持久增强。

Synapse Formation Activates a Transcriptional Program for Persistent Enhancement in the Bi-directional Transport of Mitochondria.

机构信息

Department of Neuroscience, The Scripps Research Institute-Florida, 130 Scripps Way, Jupiter, FL 33458, USA; Integrative Biology PhD Program, Charles E. Schmidt College of Science, Florida Atlantic University, Jupiter, FL 33458, USA.

Department of Neuroscience, The Scripps Research Institute-Florida, 130 Scripps Way, Jupiter, FL 33458, USA.

出版信息

Cell Rep. 2019 Jan 15;26(3):507-517.e3. doi: 10.1016/j.celrep.2018.12.073.

DOI:10.1016/j.celrep.2018.12.073
PMID:30650345
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6380353/
Abstract

Mechanisms that regulate the bi-directional transport of mitochondria in neurons for maintaining functional synaptic connections are poorly understood. Here, we show that in the pre-synaptic sensory neurons of the Aplysia gill withdrawal reflex, the formation of functional synapses leads to persistent enhancement in the flux of bi-directional mitochondrial transport. In the absence of a functional synapse, activation of cAMP signaling is sufficient to enhance bi-directional transport in sensory neurons. Furthermore, persistent enhancement in transport does not depend on NMDA and AMPA receptor signaling nor signaling from the post-synaptic neuronal cell body, but it is dependent on transcription and protein synthesis in the pre-synaptic neuron. We identified ∼4,000 differentially enriched transcripts in pre-synaptic neurons, suggesting a long-term change in the transcriptional program produced by synapse formation. These results provide insights into the regulation of bi-directional mitochondrial transport for synapse maintenance.

摘要

神经元中调节线粒体双向转运的机制尚不清楚,这种转运对于维持功能性突触连接很重要。本文中,作者发现在海兔鳃反射的感觉神经元中,功能性突触的形成会导致双向线粒体转运通量持续增强。在不存在功能性突触的情况下,cAMP 信号的激活足以增强感觉神经元中的双向转运。此外,这种运输的持续增强不依赖于 NMDA 和 AMPA 受体信号,也不依赖于突触后神经元胞体的信号,但依赖于突触前神经元中的转录和蛋白质合成。作者在突触前神经元中鉴定到约 4000 个差异富集的转录本,这表明突触形成会导致转录程序的长期改变。这些结果为突触维持中线粒体双向转运的调节提供了线索。

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