The role of Ago1 and Ago2 in neuronal development and synaptic plasticty

Ago1和Ago2在神经元发育和突触可塑性中的作用

• 批准号: RGPIN-2017-06234
• 负责人: Boehm, Jannic
• 金额: $ 1.89万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=681708
• 关键词: role; Ago1; Ago2; neuronal; development

Nerve cells communicate with each other via specialized intercellular junctions known as synapses. Synaptic plasticity, which means the strengthening and weakening of synapses, is an important feature of neuronal development as well as for learning and memory formation. Widely studied examples of vertebrate synaptic plasticity are long-term potentiation (persistent synaptic enhancement) and long-term depression (persistent synaptic weakening). Short-term events in synaptic plasticity are mediated by protein modifications, while later events require the synthesis of new proteins at the synapse. The finding that certain messenger RNAs are transported to and translated at the synapse led to the notion that long-term plasticity is implemented by spatially and temporarily restricted protein synthesis. However, the molecular signaling pathways leading to the induction of local translation remain largely elusive. ******Our research proposal will investigate the effect of NMDA-receptor activation on local protein synthesis during synaptic plasticity. We will test whether proteins that regulate local translation are affected by NMDA-receptor activation, and whether these regulators of local translation affect the outcome of long-term potentiation or long-term depression in synapses. Characterizing the different signaling pathways that are regulated during synaptic plasticity and elucidating the control mechanisms for protein synthesis at the synapse will greatly enhance our knowledge of basic mechanisms underlying neuronal development as well as learning and memory.

神经细胞通过称为突触的特殊细胞间连接相互交流。突触可塑性，即突触的增强和减弱，是神经元发育的重要特征，也是学习和记忆形成的重要特征。被广泛研究的脊椎动物突触可塑性的例子是长期增强（持续的突触增强）和长期抑制（持续的突触减弱）。突触可塑性的短期事件是由蛋白质修饰介导的，而后期事件则需要突触合成新的蛋白质。某些信使rna被转运到突触并在突触上翻译，这一发现导致了长期可塑性是通过空间和暂时限制蛋白质合成来实现的概念。然而，导致诱导局部翻译的分子信号通路在很大程度上仍然难以捉摸。******我们的研究计划将研究nmda受体激活对突触可塑性过程中局部蛋白质合成的影响。我们将测试调节局部翻译的蛋白质是否受到nmda受体激活的影响，以及这些局部翻译的调节剂是否影响突触的长期增强或长期抑制的结果。表征突触可塑性调控的不同信号通路，阐明突触蛋白质合成的控制机制，将极大地增强我们对神经元发育以及学习和记忆的基本机制的认识。