A cDNA That Suppresses MPP+ Toxicity Encodes a Vesicular Amine Transporter

Cell. 1992 Aug 21;70(4):539-51. doi: 10.1016/0092-8674(92)90425-c.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-4-phenylpyridinium / antagonists & inhibitors
  • 1-Methyl-4-phenylpyridinium / metabolism*
  • 1-Methyl-4-phenylpyridinium / toxicity
  • Adrenal Glands / chemistry
  • Amines / metabolism
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biological Transport / genetics
  • Brain Chemistry
  • CHO Cells
  • Cloning, Molecular
  • Cricetinae
  • DNA / physiology*
  • Inactivation, Metabolic
  • Models, Molecular
  • Molecular Sequence Data
  • Rats
  • Sequence Alignment
  • Vesicular Monoamine Transport Proteins

Substances

  • Amines
  • Slc18a1 protein, rat
  • Slc18a2 protein, rat
  • Vesicular Monoamine Transport Proteins
  • DNA
  • 1-Methyl-4-phenylpyridinium

Associated data

  • GENBANK/L05499
  • GENBANK/M87278
  • GENBANK/M94264
  • GENBANK/M97380
  • GENBANK/M97381
  • GENBANK/S72766
  • GENBANK/S72767
  • GENBANK/S72768
  • GENBANK/S72769
  • GENBANK/S72771