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Nogo Receptor Signaling and Function

Nogo 受体信号传导和功能

基本信息

批准号：
7161720
负责人：
MARK ALLEN BOTHWELL
金额：
$ 32.9万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-01-01 至 2008-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7161720
关键词：
Adult Affect Afferent Neurons Antibodies Antigens Antisense RNA Axon Bacteria Binding Biochemical Biological Assay Calcium Cell Line Cells Complex Coupled DNA Development Embryo Embryonic Development Expressed Sequence Tags Family member Fish Proteins Fishes Foundations Gene Family Genomics Goals Homologous Gene Image Immigration In Vitro Injection of therapeutic agent Integral Membrane Protein Ligands Link Mammalian Cell Mammals Mediating Membrane Proteins Microscopic Molecular Cloning Motor Neurons Mus Myelin NF-kappa B NGFR Protein NGFR gene Natural regeneration Neurons Orthologous Gene Pattern Polymerase Chain Reaction Population Principal Investigator Production Protein Isoforms Proteins Proteolysis Reagent Receptor Gene Receptor Signaling Regulation Signal Transduction Spinal Cord Staging Techniques Technology Testing Wild Type Mouse World Health Organization Zebrafish axon guidance base brain-derived neurotrophic factor precursor in vivo inhibitor/antagonist injured knock-down loss of function migration neural circuit neuron loss neurotrophic factor neurotropic programs protein expression receptor receptor expression relating to nervous system research study response spatiotemporal tool transcriptional coactivator p75

项目摘要

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(申请人提供)：将研究NOGO受体的信号机制和正常功能。最近的证据表明，Nogo受体(NogoR)通过与p75神经营养素受体(P75NTR)形成复合体来传递信号。存在NogoR和p75NTR的未知结构同源物。将确定这些同系物是否也形成复合体，以及它们是否通过Nogo或MAG依赖的RhoA和NF-kappaB的激活而类似于NogoR/p75NTR复合体的信号。这些研究将包括小鼠和斑马鱼NogoR同源物的分子克隆，以及在培养的哺乳动物细胞系中表达转基因的NogoR、NogoR同源物、p75NTR和p75NTR同源物。以往的研究表明，NogoR/p75NTR信号通路具有抑制损伤的成年脊髓再生的作用。据推测，NogoR/p75NTR及其同系物在胚胎发育过程中也发挥作用，引导神经轴突到达合适的靶点。这一假说将通过使用吗啡-反义RNA技术在斑马鱼胚胎中干扰这些蛋白质的表达来验证。这些操作对轴突靶向的影响将通过向胚胎中注入荧光标记DIL来评估，以允许对轴突轨迹进行显微成像。