TY - JOUR
T1 - Cloning and functional expression of a tetrabenazine sensitive vesicular monoamine transporter from bovine chromaffin granules
AU - Howell, Mike
AU - Shirvan, Anat
AU - Stern-Bach, Yael
AU - Steiner-Mordoch, Sonia
AU - Strasser, Jane E.
AU - Dean, Gary E.
AU - Schuldiner, Shimon
PY - 1994/1/24
Y1 - 1994/1/24
N2 - 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].
AB - 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].
KW - Bovine adrenal medulla
KW - Catecholamine
KW - Chromaffin granule
KW - Serotonin
KW - Tetrabenazine
KW - Vesicular monoamine transporter
KW - cDNA cloning
UR - http://www.scopus.com/inward/record.url?scp=0027955777&partnerID=8YFLogxK
U2 - 10.1016/0014-5793(94)80108-8
DO - 10.1016/0014-5793(94)80108-8
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C2 - 8307150
AN - SCOPUS:0027955777
SN - 0014-5793
VL - 338
SP - 16
EP - 22
JO - FEBS Letters
JF - FEBS Letters
IS - 1
ER -