Neuronal gene regulation by the synaptic protein RPM-1

突触蛋白 RPM-1 的神经元基因调控

• 批准号: 7093080
• 负责人: Joseph D Watson
• 金额: $ 2.59万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7093080
• 关键词: Caenorhabditis elegans; RNA interference; biological signal transduction; cell component structure /function; enzyme activity; gene expression; gene mutation; genetic mapping; genetic promoter element; genetic regulation; genetic transcription; genetically modified animals; helminth genetics; laboratory rabbit; ligase; microarray technology; mitogen activated protein kinase; motor neurons; neural transmission; predoctoral investigator; protein degradation; protein localization; protein structure function; synaptogenesis; ubiquitin

DESCRIPTION (provided by applicant): Brain function is defined by specific connections or synapses through which nerve cells communicate with each other. This activity depends on the assembly of specific molecular components on both sides of the synapse. Modulation of synaptic structure and signaling strength appears to be fundamentally important to the higher order processes of learning and memory. Recent work has revealed that synaptic function may be regulated by targeted protein degradation. Expression of the E3 ubiquitin ligase RPM-1, a proposed component of the protein degradation machinery, is required for normal synaptic morphology in the nematode, C. elegans. Genetic experiments have revealed that rpm-1 negatively regulates a MAP kinase signaling cascade. My research has shown that rpm-1 also controls expression of neuronal genes. As MAP kinase components are known to modulate synaptic plasticity through transcriptional regulation, I propose that this rpm-1 dependent pathway regulates specific genes involved in synapse formation. A collection of rpm-1 like mutants that I have isolated will be characterized to identify key components of this pathway. New and powerful microarray technology developed in this laboratory will be employed to identify rpm-1 regulated genes. Bona fide rpm-1 regulated genes will be tested genetically for roles in synapse formation and stabilization. This work should reveal genes involved in synaptogenesis.

描述（由申请人提供）：大脑功能是由神经细胞相互通信的特定连接或突触定义的。这种活动取决于突触两侧特定分子成分的组装。突触结构和信号强度的调节似乎对于学习和记忆的高级过程至关重要。最近的研究表明，突触功能可能是通过靶向蛋白质降解来调节的。 E3 泛素连接酶 RPM-1 是蛋白质降解机制的一个组成部分，其表达是线虫秀丽隐杆线虫正常突触形态所必需的。基因实验表明 rpm-1 负向调节 MAP 激酶信号级联。我的研究表明 rpm-1 还控制神经元基因的表达。由于已知 MAP 激酶成分可通过转录调节来调节突触可塑性，因此我认为这种 rpm-1 依赖性途径可调节参与突触形成的特定基因。我分离出的 rpm-1 样突变体的集合将被表征，以识别该途径的关键组成部分。该实验室开发的新型强大的微阵列技术将用于识别 rpm-1 调控基因。真正的 rpm-1 调节基因将在突触形成和稳定中的作用进行基因测试。这项工作应该揭示参与突触发生的基因。