Virus-like intercellular communication in the nervous system

神经系统中类似病毒的细胞间通讯

• 批准号: 9790850
• 负责人: Edward M Campbell
• 金额: $ 106.84万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9790850
• 关键词: Address; Biological Assay; Brain; Capsid; Cell Communication; Cell Nucleus; Cells; Cognition; Communication; Cytoplasm; Dendrites; Endogenous Retroviruses; Gene Transfer; Genes; Genetic; Goals; HIV; HIV-1; Infection; Information Storage; Integral Membrane Protein; Knowledge; Lead; Mediating; Membrane Fusion; Memory; Messenger RNA; Methodology; Methods; Modeling; Molecular; Monitor; Nervous system structure; Neuroglia; Neurons; Neurosciences; Neurotransmitter Receptor; Pathway interactions; Process; Property; Proteins; RNA; RNA-Binding Proteins; Research Personnel; Research Project Grants; Retroelements; Retrotransposon; Retroviridae; Retrovirology; Role; Signal Transduction; Structure; Synapses; Synaptic plasticity; Testing; Translating; Translations; Vesicle; Viral; Viral Genome; Virus; experience; extracellular vesicles; gag Gene Products; genetic information; innovation; insight; intercellular communication; long term memory; neuron development; novel; particle; recruit; spatiotemporal; tool; trafficking; transmission process; viral RNA

Abstract Recent studies by our group have revealed that the neuronal gene Arc, a master regulator of synaptic plasticity and information storage in the brain, acts as a repurposed retroviral Gag protein that forms capsids with the capacity to transmit genetic information between cells. These findings lead to a paradigm shift in the way we view both mechanisms of cognition and more generally how cells can signal to each other. This transformative R01 application will address these questions using a synergistic team of neuroscientists and virologists who will apply their expertise to Arc, intercellular gene transmission, and neuronal development. We will determine what genetic messages are transferred between neurons in Arc particles, how these particles enter “target” neurons to deliver their RNA cargo to cell cytoplasm, and how delivery of this cargo influences the neuronal and synaptic processes that underlie memory and cognition. The methodologies to address these questions, as well as the potential impact of the answers, make this application ideally suited to the transformative R01 mechanism.

摘要 我们课题组最近的研究表明，神经元基因Arc是一种主要的调节因子 突触的可塑性和大脑中的信息存储，作为一种重新定位的逆转录病毒Gag蛋白 这就形成了具有在细胞之间传递遗传信息的能力的衣壳。这些发现 导致我们看待认知机制和更广泛的认知机制的方式发生了范式转变 细胞之间如何相互传递信号。这款变革性的R01应用程序将解决以下问题 使用由神经学家和病毒学家组成的协同团队提出问题，这些专家将应用他们的专业知识 到Arc、细胞间基因传递和神经元发育。我们将决定什么 遗传信息在Arc颗粒中的神经元之间传递，这些颗粒是如何进入的 “靶向”神经元将其RNA货物运送到细胞质，以及如何运送这种货物 影响作为记忆和认知基础的神经元和突触过程。这个 解决这些问题的方法，以及答案的潜在影响，使 这一应用非常适合变革性的R01机构。