Regulation of the Neuronal Promoter of Calcium-Activated Potassium Channel Gene

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ABSTRACT 9724088 ATKINSON Different types of neurons must have different patterns of electical activity for the nervous system to function properly. For example, neurons that initiate movement often "fire" with high-frequency burst of action potentials, whereas neurons that control slow, rythmic behaviors may fire only slowly, but with very precise timing. A neuron's ability to generate specific activity patterns is determined by the types and numbers of ion channels it expresses. Dr. Atkinson and his students will investigate the transcriptional regulation of an ion channel gene in the fruitfly Drosophila melanogaster. The gene, called "slowpoke," produces a calcium-activated potassium channel, which is crucially involved in setting activity patterns in a variety of neurons types. The expression of any gene is controlled by specific areas of the gene called the transciptional control region. In the case of slowpoke, there are four different promoter sequences within the transciptional control region that are responsible for differential expression in different tissues. Some of the promoters alter the amount of the gene product, whereas others alter the amino acid sequence, and thus the structure, of the encoded channel. Such changes can dramatically alter a neuron's range of firing patterns. Dr. Atkinson's laboratory has cloned the entire transcriptional control region of slowpoke. They now plan to systematically introduce deletions into the region to precisely locate the transcriptional control elements responsible for expression in different neuronal subtypes. The function of these control elements will then be verified by re-introducing them as single oligonucleotide sequences, which should restore the expression pattern, if the elements have been properly identified. In the final part of the project, they will use several techniques to identify genes that produce the transcription factors that bind each of the transcription control element. The results of this work will help us understand how neurons acquire the sometimes subtle differences in ion channel number and type they need to play different functional roles.