近日，美国霍华德·休斯医学研究所David E. Clapham、Shu-Hsien Sheu等研究人员合作发现，一个血清素能的轴突-纤毛突触驱动核信号改变染色质可及性。2022年9月1日，国际知名学术期刊《细胞》发表了这一成果。
研究人员描述了轴突和初级纤毛之间的突触：轴-纤突触。在超微结构保存良好的样本上使用增强型聚焦离子束扫描电子显微镜，研究人员发现了脑干5-羟色胺能轴突和海马CA1锥体神经元的初级纤毛之间的突触。在功能上，这些纤毛富含一种纤毛限制的5-羟色胺受体，即5-羟色胺受体6（5-HTR6）。
研究人员使用一个纤毛靶向的5-羟色胺传感器，表明对5-羟色胺轴突的光和化学刺激会释放5-羟色胺到纤毛上。纤毛5-HTR6刺激激活了一个非经典的Gαq/11-RhoA途径，该途径调节核肌动蛋白，增加组蛋白乙酰化和染色质可及性。这一途径的消减会降低CA1锥体神经元的染色质可及性。作为一个接近细胞核的信号装置，轴-纤状突触缩短了神经传递的线路，从而改变突触后神经元的表观遗传状态。
据悉，轴突和树突之间的化学突触介导神经元的细胞间通讯。
附：英文原文
Title: A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility
Author: Shu-Hsien Sheu, Srigokul Upadhyayula, Vincent Dupuy, Song Pang, Fei Deng, Jinxia Wan, Deepika Walpita, H. Amalia Pasolli, Justin Houser, Silvia Sanchez-Martinez, Sebastian E. Brauchi, Sambashiva Banala, Melanie Freeman, C. Shan Xu, Tom Kirchhausen, Harald F. Hess, Luke Lavis, Yulong Li, Séverine Chaumont-Dubel, David E. Clapham
Issue&Volume: 2022/09/01
Abstract: Chemical synapses between axons and dendrites mediate neuronal intercellular communication. Here, we describe a synapse between axons and primary cilia: the axo-ciliary synapse. Using enhanced focused ion beam-scanning electron microscopy on samples with optimally preserved ultrastructure, we discovered synapses between brainstem serotonergic axons and the primary cilia of hippocampal CA1 pyramidal neurons. Functionally, these cilia are enriched in a ciliary-restricted serotonin receptor, the 5-hydroxytryptamine receptor 6 (5-HTR6). Using a cilia-targeted serotonin sensor, we show that opto- and chemogenetic stimulation of serotonergic axons releases serotonin onto cilia. Ciliary 5-HTR6 stimulation activates a non-canonical Gαq/11-RhoA pathway, which modulates nuclear actin and increases histone acetylation and chromatin accessibility. Ablation of this pathway reduces chromatin accessibility in CA1 pyramidal neurons. As a signaling apparatus with proximity to the nucleus, axo-ciliary synapses short circuit neurotransmission to alter the postsynaptic neuron’s epigenetic state.
DOI: 10.1016/j.cell.2022.07.026
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00979-5