The genes for a number of neurologically important proteins have been isolated and sequenced, and their control mechanisms are being studied. In particular, we want to understand why certain genes are expressed in neurons but not in astrocytes and vice versa. Laminin is a component of the extracellular matrix of astrocytes and promotes neurite outgrowth. In basal lamina cells laminin normally consists of 3 chains (A, Bl, B2). Using chain-specific antibodies and small cDNAs, we have shown that astrocytes make only the B2 mRNA and protein of laminin. The promoter region responsible for this specificity has been localized within 200 bp of the B2 gene. Glial fibrillary acidic protein (GFAP) is an intermediate filament protein found only in mature astrocytes. It is transcribed by RNA polymerase 11 but, in contrast to other genes, uses as promoter not only a TATA box 25 bp upstream of the start site but also a downstream element 10 to 50 bp distant. Glutamine synthetase (GS) converts glutamate to glutamine which then enters neurons and is converted to glutamate or GABA. The promoter for the GS gene contains a TATA box, 28 bp upstream from the transcription start site. Sequences with homology to cAMP and glucocorticoid response elements have also been found. Deletion mutants with the GS promoter and a CAT reporter gene have been constructed and transfected into several cell lines in order to examine the functional significance of the regulatory sequences. Genomic clones and cDNAs for the L-type calcium channel gene have been obtained. At least 4 forms of the alpha-l subunit of the channel are expressed. Hybridization experiments reveal high levels of neuron-specific calcium channel mRNA in the olfactory bulb, hippocampal CAl (ells, dentate gyrus, suprachiasmatic nucleus, and the medial preoptic nucleus. Other sites also expressed activity. Work is continuing toward isolating a human calcium gene.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Intramural Research (Z01)
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