Translation at developing synapses

突触发育过程中的翻译

• 批准号: 7579758
• 负责人: Joseph Sebeo
• 金额: $ 4.36万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7579758
• 关键词: Actins; Adhesions; Adolescent; Anisomycin; Brain-Derived Neurotrophic Factor; Cadherins; Chemicals; Cycloheximide; Dendrites; Development; Dominant-Negative Mutation; Dyes; Exposure to; Fragile X Syndrome; Hippocampus (Brain); Image; Individual; Learning; Link; Long-Term Potentiation; Maintenance; Mediating; Memory; Mental Retardation; Monitor; Morphology; N-Cadherin; Neurons; Neuropil; Process; Protein Biosynthesis; Protein Synthesis Inhibition; Protein Synthesis Inhibitors; Proteins; Protocols documentation; Regulation; Resistance; Site; Structure; Synapses; Synaptic plasticity; Translations; Work; clinically significant; depression; postsynaptic; synaptic function; synaptogenesis

DESCRIPTION (provided by the applicant) Increasing evidence has emerged supporting the idea that many more CNS synapses are made than are eventually retained, and that this phenomenon includes a process of synapse specification in which certain sites become stabilized and others are lost. Although recent work supports that young synapses are structurally and functionally distinct, the processes by which young synapses get stabilized largely remain unknown. Protein synthesis is required for mechanisms of synaptic plasticity such as long-term potentiation (LTP) or depression (LTD), as well as for learning and memory, where synapses are likely to be structurally modified. However, it is not yet known whether the stabilization of newly formed synapses requires protein synthesis. The overall hypothesis of this proposal is that newly formed synapses are labile structures that require protein synthesis for their stabilization and subsequent maintenance. Treatments that stabilize synapses should render them more resistant to such a requirement than those that destabilize synapses. Ribosomal clustering beneath synapses has been shown to be particularly prominent during development when the capacity for protein synthesis in dendritically enriched neuropil peaks; a general requirement for protein synthesis may thus operate locally. An understanding of the regulation of synaptogenesis and of the differences between dendritic and somatic regulation of protein synthesis has great clinical significance. This link is particularly clear in Fragile X mental retardation where changes in the regulation of dendritic protein synthesis have lasting consequences on synapse morphology and plasticity

描述（申请人提供） 越来越多的证据表明，支持最终保留的CNS突触更多的想法，并且这种现象包括突触规范的过程，其中某些地点稳定并且丢失了其他地点。尽管最近的工作支持年轻的突触在结构和功能上与众不同，但年轻突触稳定的过程在很大程度上尚不清楚。蛋白质合成是突触可塑性机制（例如长期增强（LTP）或抑郁症（LTD），以及学习和记忆的机制所必需的，那里的突触可能会在结构上修改。但是，尚不清楚新形成的突触的稳定是否需要蛋白质合成。该提议的总体假设是，新形成的突触是不稳定的结构，需要蛋白质综合以稳定和随后的维护。稳定突触的治疗方法应该使它们对这种需求具有更大的抵抗力。当突触下的核糖体聚集在发育过程中特别突出，当蛋白质合成的能力在树突富集的神经皮质峰中。因此，对蛋白质合成的一般需求可能在局部运作。了解突触发生的调节以及树突状和蛋白质合成的体细胞调节之间的差异具有很大的临床意义。在脆弱的X智力障碍中，这种联系尤其清楚，其中树突状蛋白质合成调节的变化对突触形态和可塑性具有持久的后果