Homology of a vesicular amine transporter to a gene conferring resistance to 1-methyl-4-phenylpyridinium

Yael Stern-Bach, Jeff N. Keen, Michal Bejerano, Sonia Steiner-Mordoch, Michael Wallach, John B.C. Findlay, Shimon Schuldiner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

The vesicular amine transporter (VAT) catalyzes transport and storage of catechol and indolamines into subcellular organelles in a wide variety of cells. It plays a central role in neurotransmission and is the primary target for several pharmacological agents. One of the drugs, reserpine, binds very tightly to the transporter and remains bound even after solubilization, a finding that has proven useful for purification of the transporter from bovine adrenal medulla in a fully functional state. The sequences of 26 N-terminal amino acids and of an additional 7-amino acid internal peptide are presented. Antibodies against a synthetic peptide based on the above sequences immunoprecipitate the transporter, confirming the conclusion that the peptide sequence is derived from bovine VAT. To our knowledge, documentation of sequences of vesicular neurotransmitter transporters has not been presented previously. In addition, the sequences obtained are highly homologous to the predicted sequence of a protein from PC12 cells that confers to Chinese hamster ovary cells resistance to 1-methyl-4-phenylpyridinium (MPP+), an agent that causes parkinsonism in model systems, confirming the hypothesis that the protein conferring resistance to MPP+ is a VAT.

Original languageAmerican English
Pages (from-to)9730-9733
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number20
DOIs
StatePublished - 15 Oct 1992

Keywords

  • Adrenal medulla
  • Catecholamines
  • Chromaffin granules
  • Indolamines
  • Parkinson disease

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