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: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=548978
• 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。主动细胞内转运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积极运输的营养因子以支持存活。 有效的转运在神经元中尤其重要，因为高度极化神经元的结构使得轴突的尖端可以距离细胞体很远，使许多细胞的成分都可以。主动运输的三个主要方面：1）细胞货物2）分子电动机3）“轨道”运动。 我的研究计划的目的是了解神经元中细胞器转运的细胞和分子基础，特别关注与轴突运输有关的运动蛋白和货物。我们通过直接成像并表征活神经细胞中的主动转运来解决这个问题。 通过研究活细胞中的动态事件，我们能够更好地分析其本质的生物学过程是动态的。 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传输并评估传输参数的变化。然后，我们使用生化方法来补充成像工作，以确认运动货车相互作用。我的研究计划最终将产生有关神经元中细胞器运输的基本问题的答案，但是由于运输到所有细胞类型的基本性质，我们的发现可能与细胞生物学的其他领域有关。 此外，怀疑在几种神经退行性疾病（例如阿尔茨海默氏症，亨廷顿和肌萎缩性侧面硬化症）中，轴突转运的破坏是一种病因，即通过了解健康的基本神经元转运，这些发现最终将有助于理解偶然神经元的问题。