Mechanisms of organelle transport in neurons

神经元细胞器运输机制

• 批准号: 327100-2011
• 负责人: Silverman, Michael
• 金额: $ 2.91万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629420
• 关键词: Mechanisms; organelle; transport; neurons

Similar to a city, nerve cells, or neurons rely on efficient transport mechanisms for development and survival. Active intracellular transport allows neurons to ship membrane components that support cell growth, signaling molecules released from the cell, and trophic factors that are actively transported from outside the cell to support survival. Efficient transport is particularly import in neurons as the architecture of the highly polarized neuron is such that the tip of the axon can be quite a distant from the cell body where many of the cell's components are made. There are three primary facets to active transport: 1) Cellular cargo 2) Molecular motors 3) "Tracks" for movement. The goal of my research program is to understand the cellular and molecular basis for organelle transport in neurons with a particular focus on the motor proteins and cargoes involved in axonal transport. We approach this problem by directly imaging and characterizing active transport in living nerve cells. By studying dynamic events in living cells we are better able to analyze a biological process that is by its nature is dynamic. For example we are able to directly measure organelle transport and assess changes in transport parameters when we alter the activity of a motor protein responsible for carrying a particular cargo. We then complement our imaging work with biochemical methods to confirm motor-cargo interactions. My research program will ultimately yield answers to basic questions concerning organelle transport in neurons, however due to fundamental nature of transport to all cell types our findings will likely be relevant to other fields of cell biology. Furthermore, axonal transport disruption is suspected as an etiology in several neurodegenerative diseases such as Alzheimer's, Huntington's, and amyotrophic lateral sclerosis, that by understanding basic neuronal transport in healthy, these findings will ultimately help in understanding problems that occur in diseased neurons.

与城市类似，神经细胞或神经元依赖于有效的运输机制来发展和生存。主动的细胞内运输允许神经元运送支持细胞生长的膜成分、从细胞释放的信号分子以及从细胞外主动运输以支持生存的营养因子。有效的运输对于神经元尤其重要，因为高度极化的神经元的结构使得轴突的尖端可能距离制造许多细胞组件的细胞体相当远。主动运输有三个主要方面：1）细胞货物2）分子马达3）运动的“轨道”。我的研究计划的目标是了解神经元中细胞器运输的细胞和分子基础，特别关注参与轴突运输的运动蛋白和货物。我们通过直接成像和表征活神经细胞的主动运输来解决这个问题。通过研究活细胞中的动态事件，我们能够更好地分析本质上是动态的生物过程。例如，当我们改变负责携带特定货物的运动蛋白的活性时，我们能够直接测量细胞器运输并评估运输参数的变化。然后，我们用生化方法补充我们的成像工作，以确认汽车与货物的相互作用。我的研究计划最终将回答有关神经元细胞器运输的基本问题，然而，由于所有细胞类型运输的基本性质，我们的发现可能与细胞生物学的其他领域相关。此外，轴突运输中断被怀疑是多种神经退行性疾病（如阿尔茨海默病、亨廷顿舞蹈病和肌萎缩侧索硬化症）的病因，通过了解健康人的基本神经元运输，这些发现最终将有助于了解患病神经元中发生的问题。