NOVEL EXTRACELLULAR PROTEINS IN AXON GUIDANCE

轴突引导中的新型细胞外蛋白

• 批准号: 7725221
• 负责人: Thomas Kidd
• 金额: $ 18.3万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725221
• 关键词: Axon; Binding; Blood Vessels; Brain; Cell Adhesion Molecules; Cells; Chemicals; Chromosomes, Human, Pair 21; Class; Computer Retrieval of Information on Scientific Projects Database; Condition; Cues; Diabetes Mellitus; Down Syndrome; Down Syndrome Cell Adhesion Molecule; Embryo; Environment; Extracellular Protein; Fiber; Funding; Genes; Genetic Screening; Grant; Individual; Institution; Knowledge; Nerve; Nervous system structure; Neurons; Patients; Phenotype; Protein Family; Proteins; Receptor Signaling; Research; Research Personnel; Resources; Signal Transduction; Source; Spinal Cord; Spinal cord injury; Surface; Symptoms; Thinking; United States National Institutes of Health; Work; axon guidance; cell type; congenital heart disorder; netrin receptor; novel; receptor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The cells of our nervous system are separated by large distances and must be connected to one another by wiring capable of carrying electrical or chemical signals. The individual fibers are known as axons, and in the early embryo they have to navigate large distances to connect up the nervous system. Cells sense their environment through proteins, known as receptors, on their surfaces that bind signals in their environment. Few signals and receptors for axons are currently known. One class is the Netrin protein family that stimulates growing nerves in the developing spinal cord, as well as other cell types including blood vessels. Through genetic screens, we have identified a novel receptor for Netrin proteins, the Down Syndrome Cell Adhesion Molecule (Dscam). In Down syndrome patients, there is an extra copy of chromosome 21. Although there are several hundred genes on chromosome 21, only a few of those genes are thought to be responsible for the majority of the symptoms. One of these genes is Dscam, a cell adhesion molecule, which allows cells to stick to one another. Dr. Kidd's work has shown that Dscam functions as a Netrin receptor to guide both nerves and cells as they migrate. Dscam also appears to be a receptor for yet to be identified cues that function in the developing nervous system. This adds to our understanding of how spinal cords and brains form, as well as having implications for spinal cord injury, as well as other conditions that impact both nerves and blood vessels such as diabetes. Knowledge that Dscam functions as both a cell adhesion molecule and as a receptor should allow for a greater understanding of how the Down Syndrome phenotype develops, including the congenital heart disease frequently seen in patients.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们神经系统的细胞相距很远，必须通过能够携带电或化学信号的线路相互连接。单个纤维被称为轴突，在早期胚胎中，它们必须移动很长的距离才能连接神经系统。细胞通过其表面的蛋白质（称为受体）感知环境，这些蛋白质与环境中的信号结合。目前已知的轴突信号和受体很少。一类是 Netrin 蛋白家族，它可以刺激发育中的脊髓以及包括血管在内的其他细胞类型的神经生长。通过基因筛选，我们发现了一种 Netrin 蛋白的新型受体，即唐氏综合症细胞粘附分子 (Dscam)。唐氏综合症患者有一个额外的 21 号染色体拷贝。尽管 21 号染色体上有数百个基因，但其中只有少数基因被认为是造成大多数症状的原因。其中一个基因是 Dscam，一种细胞粘附分子，它允许细胞彼此粘附。 Kidd 博士的研究表明，Dscam 作为 Netrin 受体发挥作用，在神经和细胞迁移时引导它们。 Dscam 似乎也是尚未确定的信号受体，这些信号在发育中的神经系统中发挥作用。这增加了我们对脊髓和大脑如何形成的理解，并对脊髓损伤以及影响神经和血管的其他疾病（如糖尿病）产生影响。了解 Dscam 既作为细胞粘附分子又作为受体的功能，有助于更好地了解唐氏综合症表型的发展过程，包括患者中常见的先天性心脏病。