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Abstract
Grant Number: 1R03MH076384-01 Project Title: Regulation of Neurotransmitter Transporter Recyclin(RMI)
PI Information: Name Title ROTHMAN, JAMES E. jr2269@columbia.edu VICE CHAIRMAN Abstract: 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.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
fluorescent dye /probe, intracellular transport, membrane transport protein, neurotransmitter transport, protein localization, technology /technique development
drug screening /evaluation, high throughput technology, membrane activity, protein kinase C, protein transport, small molecule
biotechnology
Institution: COLUMBIA UNIVERSITY HEALTH SCIENCES Columbia University Medical Center NEW YORK, NY 100323702 Fiscal Year: 2005 Department: PHYSIOLOGY AND CELLULAR BIOPHYSICS Project Start: 15-SEP-2005 Project End: 14-SEP-2006 ICD: NATIONAL INSTITUTE OF MENTAL HEALTH IRG: ZMH1