Discrete structural domains and cell-specific expression determine functional selectivity of the dopamine and norepinephrine transporters.
The successful generation and functional expression of a series of recombinant chimeric transporters, in which distinct functional properties of NET and DAT are exchanged, have allowed the assignment of a number of important functional properties of MPP+ and antidepressant-sensitive catecholamine transporters to specific domains within their primary structure. These studies are the first comprehensive structure-function analysis of members of the rapidly growing superfamily of Na+/Cl- carriers using chimeric transporters. This represents the first step in identifying the specific structural or regulatory determinants that differentiate NET and DAT. An appreciation of the potentially distinct sites for substrate recognition, translocation, and transport inhibition of NET and DAT may facilitate the development of more selective drugs for the treatment of stimulant addiction, human depression, and other affective disorders.
Buck
K J
KJ
Vollum Institute for Advanced Biomedical Research, Department of Medical Psychology, Oregon Health Sciences University, Portland 97201-3098, USA.
Lorang
D
D
Amara
S G
SG
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000737:chemistry*; D004298:Dopamine; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry*; D009638:Norepinephrine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D027981:Symporters
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011993:Recombinant Fusion Proteins; C493227:SLC6A2 protein, human; C493214:SLC6A3 protein, human; D027981:Symporters; D004298:Dopamine; D009638:Norepinephrine