title: A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter.
abstract: 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.
authors.affiliation: Department of Neurology, University of California, School of Medicine, Los Angeles 90024-1769.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Peter
authors.forename: A
authors.initials: A
authors.lastname: Roghani
authors.forename: S
authors.initials: S
authors.lastname: Schuldiner
authors.forename: G G
authors.initials: GG
authors.lastname: Privé
authors.forename: D
authors.initials: D
authors.lastname: Eisenberg
authors.forename: N
authors.initials: N
authors.lastname: Brecha
authors.forename: R H
authors.initials: RH
authors.lastname: Edwards
mesh_terms: 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
chemical_list: D000588:Amines; C493451:Slc18a1 protein, rat; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D004247:DNA; D015655:1-Methyl-4-phenylpyridinium