Intronic sequences are involved in neural targeting of human dopamine transporter gene expression.
Dopamine transporter (DAT) plays a key role in terminating synaptic dopaminergic transmission. DAT acts exclusively on the plasma membrane of presynaptic dopaminergic neurons and DAT gene is an appropriate model for the study of dopaminergic neuron-specific regulation of gene activity. DAT represents an important target for widely used neuroleptic drugs and psychostimulants and for catecholamine-selective neurotoxins. Functional abnormalities of DAT have been implicated in diverse neurologic and psychiatric disorders. Understanding the mechanisms regulating human DAT gene activity is an important step towards elucidation of the molecular bases of a number of disorders and psychostimulant drug abuse and dependence. In this study we have cloned and characterised a 7-kb segment of the human DAT gene which includes at least 4 kb of its 5'-flanking region, localised its essential, or core-promoter, and identified the region involved in regulation of DAT neurospecific expression.
Kouzmenko
A P
AP
Department of Psychiatry, University of Melbourne, Parkville, Victoria, Australia. apk@cortex.mhri.edu.au
Pereira
A M
AM
Singh
B S
BS
D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D050483:Dopamine Plasma Membrane Transport Proteins; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007438:Introns; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D009435:Synaptic Transmission; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; D008156:Luciferases