DIFFERENTIATION AND REGULATION OF GENE EXPRESSION IN ASTROCYTES AND NEURONS

我们研究基因编码蛋白质的调控

We investigate the regulation of genes encoding proteins important for astrocyte differentiation and the interaction between astrocytes and neurons. We have screened human and rat brain expression libraries for cDNAs encoding glutamine synthetase (GS), glutamate dehydrogenase (GDH) and glutaminase (GA) and determined the nucleotide sequences of the latter two. Dexamethasone induced the synthesis of GS mRNA but not of the other two enzymes. During thioacetamide induced hepatic encephalopathy in the rat, the level of glutamate decarboxylase (GAD) mRNA remained constant, that of GDH decreased whereas the levels of GA and especially GS increased; this agrees with the expectation that glutamate is scarce in astrocytes because it is rapidly converted to glutamine. We have isolated an astrocyte derived cell line which does not produce any glial fibrillary acidic protein (GFAP) or its mRNA; upon GTP deprivation by exposure to mycophenolate, both transcription and transduction are induced about 20-fold. Some major membrane proteins of brain cells were examined. One was identical or very similar to the major growth cone protein (GAP-43) by MW, isoelectric point, phosphorylation, and antibody staining. We found that this protein is glycosylated and can be labeled with iodine in whole cells, which indicates that it reaches through the membrane to the outside. Since we find the protein also in astrocytes, it may be involved in astrocyte/neuron interaction. We have also identified a neurite growth promoting factor in the extracellular matrix of astrocytes; it may be laminin because the outgrowth is at least partially inhibited by anti- laminin.