Dopamine transporter: basic science and human variation of a key molecule for dopaminergic function, locomotion, and parkinsonism.
We review the basic science of the dopamine transporter (DAT), a key neurotransmitter for locomotor control and reward systems, including those lost or deranged in Parkinson's disease (PD). Physiology, pharmaceutical features, expression, cDNA, protein structure/function relationships, and phosphorylation and regulation are discussed. The localization of DAT provides the best marker for the integrity of just the pre-synaptic dopaminergic systems that are most affected in PD. Its function is key for the actions of several toxins that provide some of the best current models for idiopathic parkinsonism, and its variation can clearly alter movement. The wealth of information about this interesting molecule that has been developed over the last 12 years has led to increased interest in DAT among workers interested in both normal and abnormal movement.
Uhl
George R
GR
Molecular Neurobiology Branch, NIDA-IRP, National Institutes of Health, Bethesda, Maryland, USA. guhl@intra.nih.gov
D000818:Animals; D003342:Corpus Striatum / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000235:genetics; D004298:Dopamine / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008124:Locomotion / Q000502:physiology*; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D009434:Neural Pathways / Q000503:physiopathology; D010300:Parkinson Disease / Q000235:genetics / Q000503:physiopathology*; D020734:Parkinsonian Disorders / Q000235:genetics / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D013378:Substantia Nigra / Q000503:physiopathology
C060858:DAT1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; D029701:Saccharomyces cerevisiae Proteins; C493215:Slc6a3 protein, mouse; D004298:Dopamine