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Wnt信号调节成人神经系统中的乙胆受体转位和突触可塑性
Michael Jensen1, Frédéric J Hoerndli, Penelope J Brockie
1Department of Biology, University of Utah, Salt Lake City, UT 84112-0840, USA.
Cell
|April 3, 2012
概括
一个Wnt信号通路通过控制乙胆受体 (AChR) 运动来调节成人神经系统中的突触强度. 这一发现揭示了体验依赖的可塑性和潜在的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 成年人的神经系统表现出可塑性,使学习和记忆成为可能,这是通过突触强度的变化来调节的.
- 控制突触信号强度的机制仍然不完全理解.
- 经验依赖的可塑性发生在神经元突触.
研究的目的:
- 定义一个调节成人神经系统突触强度的Wnt信号通路.
- 研究Wnt信号传导在调节乙胆受体 (AChR) 转移到突触中的作用.
- 为了阐明参与Wnt介导的突触可塑性中的分子组成部分.
主要方法:
- 使用Caenorhabditis elegans作为一个模型生物.
- 研究了Wnt通路组件 (CWN-2,LIN-17,CAM-1,DSH-1) 中的突变及其对ACR-16/α7 AChR局部化的影响.
- 采用光转换实验来追踪受体转位.
- 应用光遗传神经刺激来评估活动依赖的突触可塑性.
主要成果:
- Wnt通路基因的突变导致了ACR-16/α7 AChRs的亚突触积累,突触电流减少和行为缺陷.
- 光转换揭示了Wnt信号突变体中ACR-16/α7对突触的转移受损.
- 光遗传刺激表明,Wnt信号通过LIN-17/CAM-1异构受体,通过ACR-16/α7转位调解活动依赖的突触可塑性.
结论:
- 一个新的Wnt信号通路被确定为成人神经系统中突触强度的关键调节器.
- 这条通路通过调节ACR-16/α7 AChRs的转位来控制突触可塑性.
- 这些发现提供了关于学习,记忆和遗忘的分子基础的见解.
相关概念视频
Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
Cholinergic Neurons: Neurotransmission
Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
Parasympathetic Signaling
Parasympathetic signaling plays a crucial role in regulating various physiological processes. It involves the release of acetylcholine (ACh) by parasympathetic neurons, which can have localized and short-lived effects. The majority of ACh released is rapidly inactivated at the synapse by the enzyme acetylcholinesterase (AChE), which hydrolyzes Ach into choline and acetate. Additionally, the tissue cholinesterase deactivates any ACh diffusing into the surrounding tissues.
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