血清激素轴突突触驱动核信号以改变染色体的可访问性
Shu-Hsien Sheu1, Srigokul Upadhyayula2, Vincent Dupuy3
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA; Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Department of Pathology, Boston, MA, USA; Howard Huges Medical Institute, Boston Children's Hospital, Department of Cardiology, Boston, MA, USA.
Cell
|September 2, 2022
概括
研究人员发现了一种新型的轴突触,其中轴释放的血清素直接影响神经元的初级毛. 这种途径通过调节色素可访问性来改变基因表达,为神经元通信和表观遗传调节提供新的见解.
科学领域:
- 神经科学
- 细胞生物学
- 表观遗传学
背景情况:
- 传统上,神经元通过轴突和树突之间的化学突触进行通信.
- 主要的乳毛越来越多地被认为具有超越感官接收的作用,包括细胞信号传递.
- 在成熟的神经元中,初级毛的确切功能和突触连接仍然不完全理解.
研究的目的:
- 识别和描述涉及初级眼的新突触连接.
- 研究这些轴突突触中的血清素信号传递的功能作用.
- 阐明下游分子机制,通过这些信号影响神经元功能和表观遗传状态.
主要方法:
- 增强的聚焦离子束扫描电子显微镜 (FIB-SEM) 用于超结构分析.
- 开发和使用毛向的血清激素传感器.
- 通过光遗传和化学遗传来刺激血清激素轴突.
- 生物化学测试以评估G蛋白激活和下游信号通路.
- 基因组乙化和染色质可访问性的分析.
主要成果:
- 在海马CA1金字塔神经元的血清激素轴突和初级之间发现了轴突突触.
- 在这些眼中识别受受体-5-三胺受体6 (5-HTR6).
- 在刺激时向乳毛释放血清素,激活5-HTR6.
- 激活非正规的Gαq/11-RhoA通路,导致核激素调节,增加基因素乙化和染色质可访问性.
- 证据表明这种途径的切除会降低神经元中的染色质可访问性.
结论:
- 轴突触代表了一种神经元通信的新模式,直接将轴输入与初级连接起来.
- 在轴突突触中传递血清激素信号提供了一个快速的机制来改变后突触神经元的表观遗传状态.
- 这种途径绕过传统的突触传播,直接影响基因表达和染色质动态,影响神经元功能.
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