MOLECULAR BIOLOGY OF THE SYNAPSE

突触的分子生物学

• 批准号: 3075196
• 负责人: EILEEN M. LAFER
• 金额: $ 7.13万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3075196
• 关键词: SDS polyacrylamide gel electrophoresis; calpain; cell type; developmental neurobiology; embryonic stem cell; excitatory aminoacid; gene expression; genetic regulation; genetic regulatory element; genetically modified animals; hippocampus; immunocytochemistry; immunoelectron microscopy; laboratory mouse; monoclonal antibody; nerve /myelin protein; neurons; northern blottings; phosphoproteins; phosphorylation; posttranslational modifications; protein kinase; protein structure function; stereotaxic techniques; synapses; synaptogenesis; western blottings

The primary goal of the research program is to contribute to a molecular definition, and consequently deeper functional understanding of the synapse. A secondary goal which takes advantage of the reagents we are preparing in executing our primary goal is to contribute to an understanding of how the expression of neuronal specific genes are regulated spatially and temporally. Our objectives for this project period are: 1. Determination of the function of the F1-20 antigen, a novel synapse specific, developmentally regulated, neuronal specific protein in the murine CNS. Recently we have found that the F1-20 antigen is a substrate for neuronal calpain. Furthermore, we have also recently determined that the F1-20 antigen is a phosphoprotein. The possible implications of these new results for the function of the F1-20 antigen will also be explored. 2. Initial assessment of the genomic DNA sequences which are required to effect accurate cell-type specific and temporal regulation of the F1-20 gene. This will be carried out in transgenic mice, as the first step towards a longer range effort to understand the regulation of gene expression in neuronal cells. 3. Characterization of the F2-30 antigen, a novel neuronal specific protein expressed in a regionally restricted fashion within the CNS during embryogenesis. We will complete our characterization of the F2-30 cDNA, and test the hypothesis based n a homology between the deduced amino acid sequence with type III fibronectin domains that the F2-30 antigen play a role in the establishment of specific synaptic connections.

该研究计划的主要目标是为分子生物学做出贡献。 定义，从而更深入地理解 突触 第二个目标是利用我们的试剂， 在执行我们的首要目标的准备是促进一个 了解神经元特异性基因的表达是如何 在空间上和时间上进行调节。 本项目期间的目标 是：1. F1-20抗原的功能测定， 突触特异性，发育调节，神经元特异性蛋白， 小鼠中枢神经系统。 最近，我们发现F1-20抗原是一种 神经元钙蛋白酶底物。 此外，我们最近还 确定F1-20抗原是磷蛋白。 可能的 这些新结果对F1-20抗原功能的影响 也将被探索。 2. 基因组DNA序列的初步评估 这是实现准确的细胞类型特异性和时间特异性所必需的。 F1-20基因的调控。 这将在转基因小鼠中进行， 作为更长期努力理解的第一步 调节神经细胞中的基因表达。 3. 表征 F2-30抗原是一种新的神经元特异性蛋白， 在胚胎发生期间在CNS内的区域限制方式。 我们将 完成我们对F2-30 cDNA的表征，并检验假设 基于推导的氨基酸序列与III型之间的同源性， F2-30抗原在纤维连接蛋白结构域的建立中发挥作用 特定的突触连接。