Nogo Receptor Signaling and Function

Nogo 受体信号传导和功能

• 批准号: 6998453
• 负责人: MARK ALLEN BOTHWELL
• 金额: $ 33.88万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6998453
• 关键词: affinity chromatography; antisense nucleic acid; biological signal transduction; cell line; embryo /fetus tissue /cell culture; growth factor receptors; immunocytochemistry; immunologic substance development /preparation; immunoprecipitation; in situ hybridization; laboratory mouse; molecular cloning; neuronal guidance; neuronal transport; neurotrophic factors; nucleic acid sequence; polymerase chain reaction; protein isoforms; protein protein interaction; protein structure function; receptor expression; zebrafish

DESCRIPTION (provided by applicant): The signaling mechanisms and normal functions of the Nogo receptor will be investigated. Recent evidence indicates that the Nogo receptor (NogoR) signals by forming a complex with the p75 neurotrophin receptor (p75NTR). Uncharacterized structural homologs of both NogoR and p75NTR exist. It will be determined whether these homologs also form complexes and whether they signal similarly to the NogoR/p75NTR complex, via Nogo or MAG-dependent activation of RhoA and NF-kappaB. These studies will involve molecular cloning of mouse and zebrafish NogoR homologs, and expression in cultured mammalian cell lines of transfected NogoR, NogoR homolog, p75NTR and p75NTR homologs. Previous studies indicate that NogoR/p75NTR signaling functions to inhibit regeneration of the injured adult spinal cord. It is postulated that NogoR/p75NTR and homologs also function during embryonic development to guide neural axons to their appropriate targets. This hypothesis will be tested by employing morpholino-antisense RNA technology to disrupt expression of these proteins in zebrafish embryos. Effects of these manipulations on axonal targeting will be assessed by injecting the fluorescent marker Dil into embryos to allow microscopic imaging of axon trajectories.

描述（由申请人提供）：将研究NOGO受体的信号传导机制和正常功能。最近的证据表明，Nogo受体（Nogor）信号是通过与P75神经营养蛋白受体（P75NTR）形成复合物的。存在Nogor和P75NTR的未表征的结构同源物。将确定这些同源物是否还形成复合物，以及它们是否通过Nogo和NF-kappab的Nogo或MAG依赖性激活与Nogor/p75ntr复合物相似。这些研究将涉及小鼠和斑马鱼Nogor同源物的分子克隆，以及在转染的Nogor，Nogor同源物，P75NTR和P75NTR同源物的培养的哺乳动物细胞系中的表达。先前的研究表明，Nogor/P75NTR信号传导抑制受伤的成年脊髓再生。据推测，Nogor/P75NTR和同源物在胚胎发育过程中也起作用，以指导神经轴突达到其适当的靶标。该假设将通过采用吗啡抗抗反义RNA技术来破坏这些蛋白质在斑马鱼胚胎中的表达。这些操纵对轴突靶向的影响将通过将荧光标记物DIL注入胚胎以允许对轴突轨迹的微观成像进行评估。