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: 10414954
• 负责人: Edward M Campbell
• 金额: $ 106.32万
• 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/10414954
• 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 delivery; 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.

抽象的 我们小组最近的研究表明，神经元基因 Arc 是神经元的主要调节因子。 大脑中的突触可塑性和信息存储，充当重新调整用途的逆转录病毒 Gag 蛋白 形成具有在细胞之间传递遗传信息的能力的衣壳。 导致我们看待认知机制和更普遍的方式的范式转变 这个变革性的 R01 应用程序将解决这些问题。 由神经科学家和病毒学家组成的协作团队将运用他们的专业知识来提出问题 我们将确定 Arc、细胞间基因传递和神经元发育。 遗传信息在 Arc 粒子的神经元之间传递，这些粒子如何进入 “目标”神经元将其 RNA 货物递送至细胞质，以及如何递送该货物 影响记忆和认知基础的神经和突触过程。 解决这些问题的方法以及答案的潜在影响使 该应用非常适合变革性的 R01 机制。