AXONAL TRANSPORT IN THE VISUAL SYSTEM

视觉系统中的轴突运输

• 批准号: 3395230
• 负责人: JENNIFER Hart LAVAIL
• 金额: $ 12.32万
• 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 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3395230
• 关键词: autoradiography; cell cell interaction; chickens; electron microscopy; exocytosis; histochemistry /cytochemistry; immunochemistry; laboratory rat; macromolecule; membrane proteins; membrane structure; motor neurons; neuroanatomy; neurogenesis; neuromuscular junction; neuronal transport; neurotrophic factors; newborn animals; organelles; pinocytosis; retinal ganglion; synapses; transport proteins; 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，例如，激素，生长因子， 毒素、酶或病原体被神经元质膜吸收 并且必须被分选到细胞中的特定位点。 吸收和分类 上皮细胞的膜隔室是一个研究领域， 目前的调查。 然而，相对较少的注意力被 专注于神经元，尽管它们的高度细长的形状和重要的 相互依赖。 在这份授权书中， 从表面运输大分子的隔室 将检查从核周体到轴突末端。 我们假设这 通路将涉及核周膜，该膜注定被神经细胞胞吐 终端，即，神经元能够跨细胞运输。 小麦 细菌凝集素（WGA）将被用作选择性探针， 神经元膜的糖蛋白，由于其选择性结合的能力 N-乙酰葡糖胺和唾液酸残基。 碘化WGA和EM 放射自显影和免疫细胞化学技术将是主要的 用于在各种细胞中定位WGA的程序方法 神经元细胞体或轴突中的隔室。 还将寻求证据 对于WGA从神经到肌肉的细胞间转移， 神经肌肉接头 了解WGA通过神经元的细胞内路径 将为我们提供关于细胞膜内循环的新见解 神经元 这些信息不仅会增加我们对 轴突运输机制，在一般情况下，但也是细胞的基础， 许多病理状况，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， 如果我们要完全了解异常情况， 外围地（例如，周围神经病）或中枢（例如，视 青光眼中的神经压迫）。 此外，获得的关于 神经元之间的大分子转移应该阐明机制， 神经元的哪些营养因子影响肌肉细胞的发育， 神经元在发育过程中影响其他神经元。 最后，理解 预期探针运输的细胞基础将导致 改进了这些探针在神经解剖学追踪研究中的应用。