DIFFERENTIATION AND REGULATION OF GENE EXPRESSION IN ASTROCYTES AND NEURONS

星形胶质细胞和神经元基因表达的分化和调控

• 批准号: 3922579
• 负责人: E FREESE
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3922579
• 关键词: astrocytes; cell differentiation; cytogenetics; developmental neurobiology; extracellular matrix; gel electrophoresis; gene expression; genetic regulation; glial fibrillary acidic protein; glutamate decarboxylase; glutaminase; glycosylation; human tissue; immunofluorescence technique; isoelectric point; laboratory rat; laminin; membrane proteins; messenger RNA; neurons; nucleic acid probes; nucleoproteins; protein structure

We have investigated the regulation of genes of proteins typically present in astrocytes or neurons. Glutamine synthetase (GS) mRNA is made in rats as early as E14 and then increases together with corticosteroids production. The GAP-43 protein typically found in nerve growth cones apparently is exposed to the neuronal cell surface because it can be labelled with iodine, is found to a small extent in astrocytes, and may be involved in astrocyte-neuron interaction. Certainly involved in this interaction is the protein laminin which is excreted into the extracellular matrix of astrocytes and serves as a neurite outgrowth factor for both PC12 cells and primary cerebellar and cortical neurons. The glial fibrillary acidic protein (GFAP) can be induced in certain cells by guanine deprivation. The genomic DNAs of GS, GFAP and the S- 100 protein are being isolated and the promoter region will be attached to a reporter gene in order to understand the induction of these proteins and the reason why they are specifically expressed in astrocytes. The five mRNA's of the muscarinic acetylcholine receptor (ml-m5) have been individually transferred to A1-L cells where only one receptor at a time is expressed. This has enabled the analysis of the coupling of the receptor protein to different G-factors, the sensitivity to pertussis toxin, the production of phosphoinositides or cAMP, and other properties. To complement other work in the laboratory, attempts are underway to isolate the genes involved with one of the glutamate receptors.

我们通常研究了蛋白质基因的调控 存在于星形胶质细胞或神经元中。 谷氨酰胺合成酶 (GS) mRNA 早在 E14 时就在大鼠中产生，然后随着 皮质类固醇的产生。 GAP-43 蛋白通常存在于 神经生长锥显然暴露于神经元细胞 表面因为可以用碘标记，所以发现有一个小的 程度存在于星形胶质细胞中，并可能参与星形胶质细胞-神经元 相互作用。 当然参与这种相互作用的是蛋白质 层粘连蛋白被分泌到细胞外基质中 星形胶质细胞并作为 PC12 的神经突生长因子 细胞以及初级小脑和皮质神经元。 神经胶质 纤维酸性蛋白（GFAP）可以在某些细胞中被诱导 通过鸟嘌呤剥夺。 GS、GFAP 和 S- 的基因组 DNA 正在分离 100 个蛋白质，启动子区域将被分离 连接到报告基因以了解诱导 这些蛋白质的特征以及它们具有特异性的原因 在星形胶质细胞中表达。 毒蕈碱的五个 mRNA 乙酰胆碱受体（ml-m5）已单独转移 A1-L 细胞一次仅表达一种受体。 这 使得能够分析受体蛋白的偶联 对不同 G 因子、对百日咳毒素的敏感性、 磷酸肌醇或 cAMP 的产生以及其他特性。 到 补充实验室的其他工作，正在尝试 分离与其中一种谷氨酸受体有关的基因。