神经素的响应性需要一个与GPI结合的受体和Ret受体氨酸激酶
A Buj-Bello1, J Adu, L G Piñón
1School of Biological and Medical Sciences, University of St Andrews, Fife, UK.
Nature
|June 12, 1997
概括
神经素 (NTN) 和GDNF是促进神经元存活的神经营养因子. 它们通过不同的但相似的受体综合体发出信号,涉及Ret和特定的GPI连接受体,决定了连接体的特异性.
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
- 细胞生物学 细胞生物学
背景情况:
- 质细胞系衍生神经营养因子 (GDNF) 支持神经元的生存,对神经系统和脏发育至关重要.
- 通过一个受体复合体,包括Ret和GDNFR-alpha,GDNF功能.
- 神经素 (NTN) 是GDNF的一个新发现的同类物.
研究的目的:
- 为了克隆和表征Neurturin (NTN) 的受体.
- 研究NTN和GDNF在神经元生存中的受体机制.
主要方法:
- 对NTN受体的克隆,NTNR-alpha.
- 在神经元中通过微注射与Ret同时表达NTNR-alpha或GDNFR-alpha.
- 评估神经元对NTN和GDNF的生存反应.
主要成果:
- 克隆了GDNFR-alpha的同类NTNR-alpha,并发现它被广泛表达.
- NTNR-α与Ret的同时表达赋予了NTN特定的存活率.
- 与Ret同时表达的GDNFR-alpha赋予了GDNF特异性生存率.
结论:
- GDNF和NTN利用了与Ret.合作的独特的GPI链接受体 (分别是GDNFR-alpha和NTNR-alpha).
- 在GDNF/NTN信号传输中的联体特异性是由GPI相关受体组件决定的.
- 这揭示了通过多组分受体传递神经营养因子信号的保存机制.
相关概念视频
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
Enzyme-linked Receptors
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Receptor Tyrosine Kinases
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
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Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
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