Homology of a vesicular amine transporter to a gene conferring resistance to 1-methyl-4-phenylpyridinium.
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.
Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel.
Y
Y
Stern-Bach
J N
JN
Keen
M
M
Bejerano
S
S
Steiner-Mordoch
M
M
Wallach
J B
JB
Findlay
S
S
Schuldiner
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000311:Adrenal Glands / Q000737:chemistry; D000588:Amines; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002417:Cattle; D004351:Drug Resistance; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009479:Neuropeptides; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000276:immunology; D011233:Precipitin Tests; D016415:Sequence Alignment; D013572:Synaptic Vesicles / Q000378:metabolism; D050492:Vesicular Biogenic Amine Transport Proteins
D000588:Amines; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010455:Peptides; D050492:Vesicular Biogenic Amine Transport Proteins; D015655:1-Methyl-4-phenylpyridinium