Regulation of Neurotransmitter Transporter Recyclin(RMI)

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DESCRIPTION (provided by applicant): Clearance of neurotransmitter from the synaptic cleft, by high affinity transport proteins (neurotransporters), is an important stage in the regulation of neuronal signalling. A major mechanism by which neurotransporters are regulated occurs at the level of subcellular localization. Internalization of neurotransporters away from the cell surface, into an intracellular pool reduces the number of available neurotransporter molecules at the synaptic cleft. Changes that affect the regulation of neurotransporters are important in the progression of a number of neurodegenerative diseases. Here we describe an assay that can be developed into a high throughput screen to identify small molecules (drugs) that affect neurotransporter trafficking. The assay measures changes in the subcellular localization of fluorescently tagged neurotransporters in response to stimuli such as protein kinase C (PKC) signaling. Screening chemical compounds against this assay has the potential to identify small molecule effectors that can be used as tools to pharmacologically manipulation of neurotransmitter clearance. This will aid research into pathological conditions caused by alterations of neurotransporter regulation. In addition, identification of such molecules may yield compounds that can be developed into new therapeutic drugs, or provide information about potential therapeutic targets.