cAMP诱导的神经生长的转向方向的切换
1Department of Biology, University of California at San Diego, La Jolla 92093-0357, USA.
Nature
|July 17, 1997
概括
神经元循环-AMP水平决定了生长转向对指导线索的反应. 这种依赖于cAMP的开关会影响轴突在神经系统发育过程中如何导航,从而影响路径寻找.
科学领域:
- 神经科学是一个神经科学.
- 发育生物学 发展生物学
- 细胞生物学 细胞生物学
背景情况:
- 神经系统的发育依赖于精确的轴突路径寻找和成长的目标识别.
- 指导线索,如可扩散或基质结合的分子,直接生长延伸作为吸引剂或驱逐剂.
研究的目的:
- 调查循环-AMP-依赖性活动如何影响生长转向对指导线索的反应.
- 为了确定神经元循环-AMP水平是否可以改变生长转向的方向.
主要方法:
- 利用培养的Xenopus脊髓神经元观察生长的行为.
- 应用脑衍生神经营养因子 (BDNF) 和乙胆的梯度作为指导线索.
- 使用竞争性cAMP模拟物和蛋白激酶A抑制剂调节循环-AMP依赖活性.
主要成果:
- BDNF的梯度通常会吸引Xenopus脊髓神经元生长.
- 在存在cAMP模拟物或蛋白质激酶A抑制剂的情况下,相同的BDNF梯度会诱导排斥性转向.
- 乙胆诱导的转换显示出类似的cAMP-依赖开关,但神经热素-3 (NT-3) 没有.
结论:
- 神经元循环-AMP-依赖活动充当开关,逆转生长转向对特定指导线索的反应.
- 这种机制允许相同的引导分子根据神经元的内部状态引起相反的生长行为.
- 了解这种调制对于理解轴突路径和神经系统发育至关重要.
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...
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
G-Protein Gated Ion Channels
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Sensory organs,...
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,...


