The long-term objective of this project is to elucidate the molecular and cellular biology of the dopamine transporter (DAT), a plasma membrane protein thought to control synaptic levels of the neurotransmitter dopamine. Distinct alterations in DAT expression have been reported in Parkinson's disease, Alzheimer's disease, normal aging, schizophrenia. Tourette's syndrome, Lesch-Nyhan disease, and drug abuse. Another striking feature of the DAT is the extraordinary tissue specificity of expression. We have recently sequenced a portion of the human DAT gene and identified a number of potential regulatory elements. A detailed functional analysis of the DAT promoter is clearly warranted but currently hindered by a number of practical and technical considerations. The proposed experiments will establish the methodology for particle-mediated DNA transfections of organotypic rat midbrain slice cultures, such that authentic DA neurons can be transfected with DAT gene constructs and rapidly analyzed. DAT gene sequences conferring tissue specificity of expression and cocaine responsiveness will be identified. An understanding of the regulation of the DAT gene may shed light on a number of neuropsychiatric disorders.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Resource-Related Research Projects (R24)
Project #
Application #
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Wayne State University
United States
Zip Code
Rizk, Natalie N; Myatt-Jones, Javar; Rafols, Jose et al. (2007) Insulin like growth factor-1 (IGF-1) decreases ischemia-reperfusion induced apoptosis and necrosis in diabetic rats. Endocrine 31:66-71
Hill-Pryor, Crystal; Lindsey, DaShawnda; Lapanowski, Karen et al. (2006) The cardiovascular responses to mu opioid agonist and antagonist in conscious normal and obese rats. Peptides 27:1520-6
Elhamdani, Abdeladim; Azizi, Fouad; Artalejo, Cristina R (2006) Double patch clamp reveals that transient fusion (kiss-and-run) is a major mechanism of secretion in calf adrenal chromaffin cells: high calcium shifts the mechanism from kiss-and-run to complete fusion. J Neurosci 26:3030-6
Elhamdani, Abdeladim; Azizi, Fouad; Solomaha, Elena et al. (2006) Two mechanistically distinct forms of endocytosis in adrenal chromaffin cells: Differential effects of SH3 domains and amphiphysin antagonism. FEBS Lett 580:3263-9
Bannon, Michael J (2005) The dopamine transporter: role in neurotoxicity and human disease. Toxicol Appl Pharmacol 204:355-60
Wang, Jun; Bannon, Michael J (2005) Sp1 and Sp3 activate transcription of the human dopamine transporter gene. J Neurochem 93:474-82
Michelhaugh, Sharon K; Vaitkevicius, Henrikas; Wang, Jun et al. (2005) Dopamine neurons express multiple isoforms of the nuclear receptor nurr1 with diminished transcriptional activity. J Neurochem 95:1342-50
Rizk, Natalie; Dunbar, Joseph C (2004) Insulin-mediated increase in sympathetic nerve activity is attenuated by C-peptide in diabetic rats. Exp Biol Med (Maywood) 229:80-4
Tisdale, Ellen J; Kelly, Carmen; Artalejo, Cristina R (2004) Glyceraldehyde-3-phosphate dehydrogenase interacts with Rab2 and plays an essential role in endoplasmic reticulum to Golgi transport exclusive of its glycolytic activity. J Biol Chem 279:54046-52
Rao, Sumangala P; McRae, Crystal; Lapanowski, Karen et al. (2003) Insulin mediated hemodynamic responses in spontaneous hypertensive rats (SHRs): effect of chromosome 4 gene transfer. Clin Exp Hypertens 25:131-42

Showing the most recent 10 out of 100 publications