AXONAL TRANSPORT IN THE VISUAL SYSTEM

视觉系统中的轴突运输

• 批准号: 3395228
• 负责人: JENNIFER Hart LAVAIL
• 金额: $ 11.1万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3395228
• 关键词: autoradiography; cell cell interaction; electron microscopy; exocytosis; histochemistry /cytochemistry; immunochemistry; macromolecule; membrane structure; motor neurons; neuroanatomy; neuromuscular junction; neuronal transport; neurotrophic factors; newborn animals; organelles; pinocytosis; retinal ganglion; synapses; visual pathways

Important nutrients or effector molecules, e.g., hormones, growth factors, toxins, enxymes or pathogens, are taken in by the neuronal plasma membrane and must be sorted to specific sites in the cell. Uptake and sorting of membrane compartments by epithelial cells is a research field of intense current investigation. However, relatively little attention is being focused on neurons, despite their highly elongated shape and vital interdependence on one another. In this grant the identity of the membrane compartments that transport macromolecules from the surface of the perikaryon to the axon terminal will be examined. We hypothesize that this path will involve perikaryal membrane that is fated for exocytosis by nerve terminals, i.e., neurons are capable of transcellular transport. Wheat germ agglutinin (WGA) will be used as a selective probe for the glycoproteins of neuronal membranes, due to its ability to bind selectively to N-acetyglucosamine and sialic acid residues. Iodiated WGA and EM autoradiography as well as immunocytochemical techniques will be the prime methods of procedure used to localize the WGA in various cellular compartments in the neuron cell body or axon. Evidence will also be sought for the intercellular transfer of WGA from nerve to muscle at the neuromuscular junction. Understanding the intracellular path followed by WGA through the neuron will provide us with new insight about the circulation of membrane within neurons. The information will also increase our understanding not only of axonal transport mechanisms, in general, but also of the cellular basis for many pathological conditions, including pathological intoxications with environmental toxins. We need to know the normal patterns of organelle and membrane sorting if we are to understand fully abnormal situations, either peripherally (e.g., peripheral neuropathies) or centrally (e.g., optic nerve compression in glaucoma). Moreover, information gained about the transfer of macromolecules between neurons should clarify the mechanisms by which trophic factors from neurons influence muscle cell development or neurons influence other neurons during development. Lastly, understanding the cellular basis for the transport of probes is expected to lead to the improved application of these probes in neuroanatomical tracing studies.

重要的营养素或效应分子，如激素、生长因子、 毒素、酶或病原体被神经细胞质膜吸收。 并且必须被分类到单元中的特定位置。吸收和分类 由上皮细胞构成的膜室是目前研究的热点领域 目前的调查。然而，相对较少的关注是 专注于神经元，尽管它们高度拉长的形状和重要的 相互依存。在该授权书中，膜的身份 从表面输送大分子的隔间 将对轴突末端的核周进行检查。我们假设这是 路径将涉及神经注定要进行胞吐的细胞膜。 终末，即神经元，能够跨细胞运输。小麦 细菌凝集素(WGA)将作为选择性探针用于检测 神经细胞膜的糖蛋白，因为它具有选择性结合的能力 N-乙酰氨基葡萄糖和唾液酸残基。加碘的WGA和EM 放射自显影和免疫细胞化学技术将是最好的 WGA在不同细胞中定位的程序方法 神经元细胞体或轴突中的隔室。还将寻找证据 用于WGA从神经到肌肉的细胞间转移 神经肌肉接头。 了解WGA穿过神经元的细胞内路径 将为我们提供关于体内膜循环的新见解 神经元。这些信息不仅会增加我们对 轴突运输机制，一般，但也是细胞基础的 许多病理情况，包括病理性中毒 环境毒素。我们需要知道细胞器的正常模式和 膜分选如果我们要充分了解异常情况，也 外周(例如，外周神经病)或中枢(例如，视神经疾病 神经压迫青光眼)。此外，获得的关于 大分子在神经元之间的转移应该通过以下方式阐明机制 来自神经元的哪些营养因子影响肌肉细胞的发育或 神经元在发育过程中影响其他神经元。最后，理解 探针运输的细胞基础预计将导致 改进了这些探针在神经解剖示踪研究中的应用。