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