Genes Essential To Motor Axon Guidance in Drosophila

果蝇运动轴突引导所必需的基因

• 批准号: 7435315
• 负责人: David L. Van Vactor
• 金额: $ 37.17万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7435315
• 关键词: Actins; Architecture; Axon; Behavior; Binding; Biochemistry; Brain; Cells; Cellular biology; Class; Complex; Data; Defect; Development; Dissection; Drosophila genus; Dynein ATPase; Employee Strikes; Essential Genes; Future; Genes; Genetic; Glues; Growth Cones; Human; Image; Lateral; Ligands; Link; Localized; Logic; Mediating; Membrane; Membrane Protein Traffic; Microfilaments; Microtubule-Associated Proteins; Microtubules; Modification; Molecular; Motor; Mutation; Natural regeneration; Nervous system structure; Neuraxis; Ocular orbit; Pathway interactions; Pattern; Phenotype; Phosphorylation; Play; Plus End of the Microtubule; Polymers; Positioning Attribute; Protein Tyrosine Kinase; Proteins; Pyrococcus kodakaraensis TIP protein; Regulation; Research Personnel; Role; Series; Shapes; Signal Pathway; Signal Transduction; Specificity; Surveys; Therapeutic; Translating; Xenopus; axon growth; axon guidance; cell motility; directional cell; dynactin; interest; mutant; myosin VI; nervous system development; nervous system disorder; novel; protein function; receptor; relating to nervous system

DESCRIPTION (provided by applicant): The intracellular mechanisms that control growth cone navigation to appropriate target cells are required to build networks of functional neural connections during nervous system development and regeneration. Our long-standing interest in the cytoskeletal signaling machinery downstream of multiple guidance receptors has led us to a series of conserved microtubule-associated proteins that appear to mediate different types of guidance behavior. Analysis of the effector protein CLASP has defined a pathway from the repellent factor Slit and its Roundabout receptors, to the Abelson tyrosine kinase, to CLASP, as a means of impeding microtubule and leading edge advance. How Abl acts to coordinate microfilament and microtubule dynamics, and control the activity of CLASP or its associated partners is unknown. Preliminary data indicates that several proteins directly or indirectly linked to CLASP are required for accurate midline repulsion, whereas other microtubule effector proteins appear to play distinct roles in early axon guidance decisions. We will use a combination of genetics, cell biology and biochemistry to determine each protein's function in axon guidance and to dissect the signaling mechanisms that regulate the key effector activities.

描述（由申请人提供）：在神经系统发育和再生期间，需要控制生长锥导航至适当靶细胞的细胞内机制来构建功能性神经连接网络。我们长期以来对多种指导受体下游的细胞骨架信号机制的兴趣使我们发现了一系列保守的微管相关蛋白，这些蛋白似乎介导了不同类型的指导行为。对效应蛋白CLASP的分析已经确定了从驱避因子Slit及其Roundabout受体到Abelson酪氨酸激酶再到CLASP的通路，作为阻碍微管和前沿进展的手段。Abl如何协调微丝和微管动力学，并控制CLASP或其相关伙伴的活动是未知的。初步数据表明，几种蛋白质直接或间接地连接到CLASP需要准确的中线排斥，而其他微管效应蛋白似乎发挥不同的作用，在早期轴突的指导决策。我们将结合遗传学、细胞生物学和生物化学来确定每种蛋白质在轴突导向中的功能，并剖析调节关键效应物活动的信号传导机制。