Cloning and functional expression of a tetrabenazine sensitive vesicular monoamine transporter from bovine chromaffin granules

Mike Howell, Anat Shirvan, Yael Stern-Bach, Sonia Steiner-Mordoch, Jane E. Strasser, Gary E. Dean, Shimon Schuldiner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Using oligonucleotide primers derived from the vesicular monoamine transporters sequences, a cDNA predicted to encode the bovine chromaffin granule amine transporter has been cloned (b-VMAT2). Surprisingly, its structure is more similar to the rat brain transporter (VMAT2), than to the rat adrenal counterpart (VMAT1). Unlike rat VMAT1, bovine VMAT2 appears to be expressed both in the adrenal medulla and the brain, as judged by Northern analysis. After modification/deletion of the seven amino acids at the N-terminus of the protein it was expressed in a functional form. The order of affinity of the bovine VMAT2 transporter to substrates is: serotonin>dopamine = norepinephrine>epinephrine. Also, the recombinant bovine adrenal transporter is highly sensitive to tetrabenazine, in sharp contrast to the rat adrenal transporter. The findings indicate, therefore, a clear species variation in which structure and function of the bovine adrenal transporter resemble the rat brain protein, while its tissue distribution is distinct from both types of rat proteins. In addition, the predicted protein sequence is identical to the experimentally determined N-terminus sequence of the purified vesicular amine transporter [Stern-Bach et al. (1992) Proc. Natl. Acad. Sci. USA 89, 9730-9733].

Original languageAmerican English
Pages (from-to)16-22
Number of pages7
JournalFEBS Letters
Volume338
Issue number1
DOIs
StatePublished - 24 Jan 1994

Keywords

  • Bovine adrenal medulla
  • Catecholamine
  • Chromaffin granule
  • Serotonin
  • Tetrabenazine
  • Vesicular monoamine transporter
  • cDNA cloning

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