Mechanisms of Neurotrophin and Ephrin Signal Integration

神经营养素和肝配蛋白信号整合的机制

• 批准号: 8733290
• 负责人: CHERYL F DREYFUS
• 金额: $ 40.4万
• 依托单位: RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-03 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8733290
• 关键词: Adaptor Signaling Protein; Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Ankyrin Repeat; Autistic Disorder; Behavior; Biochemical; Biological; Biological Assay; Brain-Derived Neurotrophic Factor; Cell Communication; Cells; Complex; Data; Degenerative Disorder; Development; Early treatment; Eph Family Receptors; Ephrins; Event; Growth; Growth Cones; Hippocampus (Brain); Instruction; Integral Membrane Protein; Learning; Ligands; Mediating; Membrane; Memory; Modification; Molecular; Morphology; Nerve Growth Factor Receptors; Nervous system structure; Neuraxis; Neurodegenerative Disorders; Neurons; Outcome; Parkinson Disease; Pattern; Phosphorylation; Play; Proteins; Receptor Signaling; Regulation; Research; Research Personnel; Role; Second Messenger Systems; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Signaling Protein; Spinal cord injury; Synapses; Synaptic Transmission; Synaptic plasticity; System; Vertebral column; axon growth; axon guidance; density; developmental disease; domain mapping; extracellular; gain of function; loss of function; neurotrophic factor; novel; polypeptide; receptor; relating to nervous system; second messenger; transcriptional coactivator p75

Cell-cell communication represents the combined effects of multiple polypeptide factors. To explain complex effects in the nervous system requires an understanding of how local circuits and signal transduction pathways are integrated. Ephrins and Neurotrophins display both rapid and slower long lasting effects that require receptor signaling to proceed in a linear stop-wise fashion, but also influence each other, either directly or through signaling intermediates. Regulation of Ephrins and Neurotrophins is likely to be determined by the additive effects of their receptors and the duration of second messengers and phosphorylation events. Interactions between Ephrin and Neurotrophin receptors and downstream signaling proteins provide a mechanism for merging the actions of different ligand-receptor systems in order to achieve novel cellular outcomes. This subproject will focus on a set of downstream substrates that are used by both Ephrin and Neurotrophin receptors. The hypothesis is that cooperativity and antagonism between these two different transmembrane protein systems provide additional mechanisms for extracellular signaling. The proposed research is relevant to the understanding and treatment of early developmental disorders, such as autism, and neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases and amyotrophic lateral sclerosis, which depend upon the actions of Ephrins and Neurotrophins for correct developmental patterning and circuit formation.

细胞 - 细胞通信代表了多种多肽因子的综合作用。解释复杂 神经系统中的影响需要了解本地电路和信号转导的方式 途径已集成。 ephrins和neurotrophins表现出快速和较慢的持久作用 需要以线性停止方式进行受体信号传导，但同时也相互影响 直接或通过信号中间体。源自源自晶状体和神经营养蛋白的调节可能是 取决于其受体的添加效应以及第二信使的持续时间 磷酸化事件。 ephrin和神经营养蛋白受体与下游信号之间的相互作用 蛋白质提供了合并不同配体受体系统作用的机制，以便 实现新颖的细胞结局。该子标记将重点放在一组使用的下游基板上 通过ephrin和神经营养蛋白受体。假设是 这两个不同的跨膜蛋白系统提供了细胞外的其他机制 信号。拟议的研究与对早期发展的理解和治疗有关 自闭症和神经退行性疾病等疾病，例如帕金森氏症和阿尔茨海默氏病 和肌萎缩性侧索硬化症，取决于源自源自源自的作用和神经营养蛋白正确 发展模式和电路形成。