The dopamine (DA) transporter (DAT) is critical in the re-uptake of DA into presynaptic neurons and the termination of dopamine signaling. Alterations in DA signaling is evident in several disease pathologies including ADHD, Parkinson's disease and schizophrenia. Recently, it has been shown that intracellular proteins interact with and affect the localization and function of DAT. As such, we hypothesize that DAT exists in a protein complex that regulates the activity of the transporter. To test this hypothesis we will take advantage of the model system C. elegans to test candidate regulatory proteins for DAT and identify novel proteins that associate with the transporter. The C. elegans dopamine transporter DAT-1) shows a 45% homology to the human transporter, with a sensitivity to amphetamines, cocaine, and other biogenic amine transporter antagonists. In my proposal, I build on recent studies by our laboratory on DAT-1 to: 1) determine the expression level and localization of DAT-1, 2) characterize the interactions of the C. elegans PICK1 homologue (Y57G11C.22) with DAT-1 and, 3) identify novel proteins that interact with the C. elegans dopamine transporter. These studies will increase our understanding of intrinsic modulatory influences controlling DA signaling in vivo and in disease states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS046237-01
Application #
6645780
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Sheehy, Paul A
Project Start
2003-07-01
Project End
2006-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
1
Fiscal Year
2003
Total Cost
$24,910
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Pharmacology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212