9407849 Neckameyer ABSTRACT Synaptic transmission is critically dependent on the concentrations of neurotransmitter at the synaptic cleft. Upon release of the neurotransmitter at the cleft, neurotransmitter transporters contribute to the removal of transmitter into the presynaptic terminal. This limits the duration of the neurotransmitter action, and is thought to play a major role in maintaining neurotransmitter availability at a variety of synapses. The precise molecular mechanisms which regulate the activity of the neurotransmitter transporters are only beginning to be elucidated. Moreover, such work has not yet addressed the developmental and functional significance of perturbing these mechanisms in vivo. This application proposes to build upon our recent cloning of Drosphila neurotransmitter transporter cDNAs to examine the regulation of these important proteins. The choice of Drosophila enables us to bring to bear some of the unique advantages of this model system (such as the facility in generating both transgenic animals as well as mutations specific to genetic loci) on these important questions. These studies will take advantage of recombinant DNA methodology to (1) identify the specific neurotransmitter substrate for each of the transporters isolated thus far, and (2) to initiate a molecular genetic analysis of the transporter loci. These initial studies will lay the groundwork for future experiments that will assess the developmental and functional consequences in vivo of perturbing reuptake regulatory mechanisms by introducing altered transporter genes into the genome of Drosphila. These studies will increase our comprehension of the role that neurotransmitter transporters play in synaptic transmission.
