Functional identification of a vesicular acetylcholine transporter and its expression from a "cholinergic" gene locus.
The vesicular acetylcholine transporter (VAChT) has been identified and characterized based on the acquisition of high affinity vesamicol binding and proton-dependent, vesamicol-sensitive acetylcholine accumulation by a fibroblast cell line transfected with a clone from a rat pheochromocytoma cDNA library encoding this protein. The distribution of VAChT mRNA coincides with that reported for choline acetyltransferase (ChAT), the enzyme required for acetylcholine biosynthesis, in the peripheral and central cholinergic nervous systems. A human VAChT cDNA was used to localize the VAChT gene to chromosome 10q11.2, which is also the location of the ChAT gene. The entire sequence of the human VAChT cDNA is contained uninterrupted within the first intron of the ChAT gene locus. Transcription of VAChT and ChAT mRNA from the same or contiguous promoters within a single regulatory locus provides a previously undescribed genetic mechanism for coordinate regulation of two proteins whose expression is required to establish a mammalian neuronal phenotype.
Erickson
J D
JD
Section on Molecular Neuroscience, National Institute of Mental Health, Bethesda, Maryland 20892.
Varoqui
H
H
Schäfer
M K
MK
Modi
W
W
Diebler
M F
MF
Weihe
E
E
Rand
J
J
Eiden
L E
LE
Bonner
T I
TI
Usdin
T B
TB
D000109:Acetylcholine / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000235:genetics; D002799:Cholinergic Fibers / Q000378:metabolism*; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D018076:DNA, Complementary; D006801:Humans; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D016716:PC12 Cells; D011487:Protein Conformation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D018076:DNA, Complementary; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C493459:SLC18A3 protein, human; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine