A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter.
Classical neurotransmitters are transported into synaptic vesicles so that their release can be regulated by neural activity. In addition, the vesicular transport of biogenic amines modulates susceptibility to N-methyl-4-phenylpyridinium (MPP+), the active metabolite of the neurotoxin N-methyl-1,2,3,6-tetrahydropyridine that produces a model of Parkinson's disease. Taking advantage of selection in MPP+, we have used gene transfer followed by plasmid rescue to identify a cDNA clone that encodes a vesicular amine transporter. The sequence predicts a novel mammalian protein with 12 transmembrane domains and homology to a class of bacterial drug resistance transporters. We have detected messenger RNA transcripts for this transporter only in the adrenal gland. Monoamine cell populations in the brain stem express a distinct but highly related protein.
Liu
Y
Y
Department of Neurology, University of California, School of Medicine, Los Angeles 90024-1769.
Peter
D
D
Roghani
A
A
Schuldiner
S
S
Privé
G G
GG
Eisenberg
D
D
Brecha
N
N
Edwards
R H
RH
D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000633:toxicity; D000311:Adrenal Glands / Q000737:chemistry; D000588:Amines / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport / Q000235:genetics; D001923:Brain Chemistry; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D004247:DNA / Q000502:physiology*; D008658:Inactivation, Metabolic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051381:Rats; D016415:Sequence Alignment; D050493:Vesicular Monoamine Transport Proteins
D000588:Amines; C493451:Slc18a1 protein, rat; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D004247:DNA; D015655:1-Methyl-4-phenylpyridinium