Molecular mechanisms of dendritic tiling in Drosophila

果蝇树突平铺的分子机制

• 批准号: 7109545
• 负责人: YI ZHENG
• 金额: $ 5.2万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7109545
• 关键词: Drosophilidae; active sites; biological signal transduction; dendrites; developmental genetics; developmental neurobiology; enzyme activity; neurogenesis; neurogenetics; phosphorylation; postdoctoral investigator; protein binding; protein kinase; protein structure function

DESCRIPTION (provided by applicant): For a nervous system to be wired into proper neuronal circuits, the axons need be guided to the correct targets and the dendrites must have the correct branching patterns. Relative little is known about the molecular basis for dendrite development. Recently, two evolutionarily conserved proteins, Trc and Fry, have been identified as essential players for dendritic branching and tiling. The goal of the proposal is to identify and characterize additional gene products in this core signaling program. Several lines of evidence suggest that Mats/Dmob1, a member of the conserved Mob family of proteins, may be involved in the Trc/Fry signaling pathway. I propose to test the hypothesis that Mats/Dmob1 functions as an activator to regulate Trc kinase activity. Genetic and biochemical analysis will also be performed to identify and characterize additional molecules implicated in the Trc/Fry signaling pathway in dendrite development. Given the strong conservation of this pathway across phylogeny, it is likely that our experiments will provide new insights into the mechanisms underlying dendrite development in vertebrates and may also lead to improved diagnosis and therapeutics of nervous system disorders caused by abnormal dendrites formation.

描述（由申请人提供）：为了将神经系统连接到正确的神经元回路中，轴突需要被引导到正确的目标，并且树突必须具有正确的分支模式。关于树突发育的分子基础知之甚少。最近，两种进化上保守的蛋白质 Trc 和 Fry 已被确定为树突分支和平铺的重要参与者。该提案的目标是识别和表征该核心信号转导程序中的其他基因产物。多项证据表明，Mats/Dmob1（保守的 Mob 蛋白家族成员）可能参与 Trc/Fry 信号通路。我建议检验 Mats/Dmob1 作为调节 Trc 激酶活性的激活剂的假设。还将进行遗传和生化分析，以识别和表征树突发育中与 Trc/Fry 信号通路有关的其他分子。鉴于该途径在整个系统发育过程中具有很强的保守性，我们的实验很可能将为脊椎动物树突发育的机制提供新的见解，并且还可能改善由异常树突形成引起的神经系统疾病的诊断和治疗。