Dopamine transporter

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solute carrier family 6 (neurotransmitter transporter, dopamine), member 3
Identifiers
Symbol	SLC6A3 DAT1
HUGO	11049
Entrez	6531
OMIM	126455
RefSeq	NM_001044
UniProt	Q01959
Other data
Locus	Chr. 5 p15.3

The dopamine transporter or DAT is a monoamine transporter that is specific for clearing the neurotransmitter dopamine from the synaptic cleft and into a glial cell or the presynaptic neuron.

1 Location and distribution
2 Function
- 2.1 Action of DAT-blockers
3 See also
4 References
5 External links

[edit] Location and distribution

In the striatum, DAT is localized in the plasma membrane of axon terminals. Double immunocytochemistry demonstrated DAT colocalization with two other markers of nigrostriatal terminals, tyrosine hydroxylase and D2 dopamine receptors. The latter was thus demonstrated to be an autoreceptor. Labeled striatal terminals formed symmetrical synapses with spines, dendrites, and perikarya. Regional distribution of DAT was found in areas with established dopaminergic circuitry, e.g., mesostriatal, mesolimbic, and mesocortical pathways. Mesencephalic DAT-immunoreactivity was enriched in the dendrites and cell bodies of neurons in the substantia nigra pars compacta and ventral tegmental area. Staining in the striatum and nucleus accumbens was dense and heterogeneous. DAT was not identified within any synaptic active zones, however, even using serial section analysis. These results suggest that striatal dopamine reuptake may occur outside of synaptic specializations once dopamine diffuses from the synaptic cleft. In the substantia nigra, DAT appears to be specifically transported into dendrites, where it can be found in smooth endoplasmic reticulum, plasma membrane, and pre- and postsynaptic active zones. These localizations suggest that DAT modulates the intracellular and extracellular dopamine levels of nigral dendrites. Within the perikarya of pars compacta neurons, DAT was localized primarily to rough and smooth endoplasmic reticulum, Golgi complex, and multivesicular bodies, identifying probable sites of synthesis, modification, transport, and degradation.

[edit] Function

The dopamine transporter serves to remove excess dopamine from the synaptic cleft, effectively ending the signaling of the neurotransmitter and recycling the transmitter.

[edit] Action of DAT-blockers

Cocaine and methylphenidate block the action of the dopamine transporter and, to a lesser extent, of other monoamine transporters. This causes an overload of dopamine in the extracellular space (synaptic cleft), since the neurotransmitter cannot be cleared away after its release.

[edit] See also

[edit] References

Steven M. Hersch, Hong Yi, Craig J. Heilman, Robert H. Edwards, and Allan I. Levey. Subcellular Localization and Molecular Topology of the Dopamine Transporter in the Striatum and Substantia Nigra. Journal of Comparative Neurology 388:211–227 (1997).
Brian J. Ciliax, Genny W. Drash, Julie K. Staley, Sharon Haber, Catherine J. Mobley, Gary W. Miller, Elliott J. Mufson, Deborah C. Mash, and Allan I. Levey. Immunocytochemical localization of the dopamine transporter in human brain. The Journal of Comparative Neurology 409:38-56 (1999).