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Protein A002796
Author-entered Data
V1.0, Peer Reviewed
Published 16 May 2008
Automated Data
Not Reviewed
As At Publication
Automated Data
Not Reviewed
Latest from 6 Jun 2014

UCSD Nature Molecule Pages
Published online: 16 May 2008 | doi:10.1038/mp.a002796.01

VAChT

Basis Sequence: Mouse

Vania F Prado1, Marco A Prado2, Stanley M Parsons3

1Biochemistry, Universidade Federal de Minas Gerais, Minas Gerais 31270-010, BR. 2Robarts Research Institute, University of Western Ontario, ON N6A 5K8, CA. 3Department of Chemistry and Biochemistry, University of California, CA 93106-9510, US.

Correspondence should be addressed to Marco A Prado: mprado@robarts.ca


The gene for vesicular acetylcholine transporter (VAChT) is found in the first intron of the gene for choline acetyltransferase. This nested gene arrangement is unique in animals and links the expression of the two proteins in the nervous system. VAChT contains twelve transmembrane segments surrounding a central transport channel. It is responsible for packaging acetylcholine (ACh) into synaptic vesicles. This transporter is rate limiting for ACh release from the nerve terminal. A V-ATPase provides luminal protons that VAChT exchanges with cytoplasmic ACh to drive the formation of a 100-fold concentration gradient. ACh transport follows classical steady-state initial-velocity kinetics with a Michaelis constant of 0.6-1.0 mM. A synthetic molecule named vesamicol is a noncompetitive inhibitor of transport, exhibiting a dissociation constant of ~ 20 nM. The ACh and vesamicol binding sites are probably in the central transport channel located close to, but separate from each other. Because it readily passes through the blood-brain barrier and binds to VAChT with high affinity, the vesamicol family of compounds is being developed to image fields of cholinergic terminals in vivo, particularly in brain. Potential applications include diagnosis of Alzheimer's disease. In mammals, immunohistochemical analyses indicate that VAChT is present in cholinergic cell bodies, fibers and terminals. VAChT also is in non-neural tissues, including the immune system. In non-neuronal cells, choline acetyltransferase can be expressed independently from VAChT. Accurate targeting of VAChT to synaptic-like vesicles in cultured cells relies mainly on a dileucine-containing motif present in the C-terminal tail. The amount of VAChT expression regulates filling of vesicles, physical endurance and cognitive behavior in mice.

Alternative names for this molecule: Slc18a3; Solute carrier family 18 (vesicular acetylcholine), member 3; Solute carrier family 18 (vesicular monoamine), member 3; Solute carrier family 18, member 3; VAChT; VACHT; VAT

Transition Network Graph This molecule exists in 15 states, has 16 transitions between these states and has 4 transporter functions.

[map] View high resolution network map