香味受体衍生的cAMP信号直接向轴突准
Takeshi Imai1, Misao Suzuki, Hitoshi Sakano
1Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0032, Japan.
概括
循环腺单酸盐 (cAMP) 信号,而不是气味受体 (OR) 本身,引导嗅觉感官神经元 (OSN) 轴突. 这些cAMP信号对于正确向嗅球的轴突投射至关重要.
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
- 感官系统 感官系统
背景情况:
- 嗅觉神经元 (OSN) 上的气味受体 (OR) 对于检测气味至关重要.
- OSN轴突必须精确地导航到嗅球内的目标部位,以便进行适当的嗅觉处理.
- 这种精确的轴突向背后的分子机制尚未完全理解.
研究的目的:
- 研究周期性腺单酸盐 (cAMP) 信号在OR介导的轴突引导中的作用.
- 为了确定OR分子是否直接指导轴突投射,或者下游信号是否负责.
- 确定参与嗅觉轴突向的cAMP通路的关键组件.
主要方法:
- 在哺乳动物中对ORs,G蛋白,cAMP依赖蛋白激酶和cAMP反应元素结合蛋白进行基因操纵.
- 用遗传模型分析嗅球中OSNs的轴突投射模式.
- 评估目标目的地沿着嗅球前后轴的变化.
主要成果:
- 影响cAMP信号通路的遗传变化,包括G蛋白和蛋白激酶等组件,显著改变了OSN轴突投射部位.
- 这些操纵导致嗅球内前后准的转移.
- 该研究表明,cAMP信号水平与轴突准的精度之间存在明显的相关性.
结论:
- 循环腺单酸盐 (cAMP) 信号传递对于嗅觉球中的嗅觉神经元 (OSN) 轴突的正确向至关重要.
- 这些发现表明,OR衍生的cAMP信号,而不是OR分子的直接作用,是OSN轴突目的地的主要决定因素.
- 这项研究阐明了一种关键的分子机制,它控制了嗅觉系统中神经电路的形成.
相关概念视频
Intracellular Signaling Cascades
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
Intracellular Signaling Cascades
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
Amplifying Signals via Second Messengers
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...


