Disease relevance of Slc18a3

• 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 [1].
• Subpopulations of rat dorsal root ganglion neurons express active vesicular acetylcholine transporter [2].
• Differential effects of traumatic brain injury on vesicular acetylcholine transporter and M2 muscarinic receptor mRNA and protein in rat [3].
• In these studies, we tested the hypothesis that choline acetyltransferase (ChAT) and vesicular ACh transporter (VAChT) mRNAs are expressed in the CB and that mRNA levels would increase with postnatal maturation or exposure to hypoxia [4].

High impact information on Slc18a3

• In PC12 cells, the vesicular acetylcholine transporter (VAChT) localizes preferentially to synaptic-like microvesicles (SLMVs), whereas the closely related vesicular monoamine transporters (VMATs) localize preferentially to large dense core vesicles (LDCVs) [5].
• We now show that VAChT undergoes regulated phosphorylation by protein kinase C on a serine (Ser-480) five residues upstream of the dileucine motif [5].
• VAChT and the VMATs contain COOH-terminal, cytoplasmic dileucine motifs required for internalization from the plasma membrane [5].
• Since previous work has suggested that VAChT expression confers little if any transport activity in non-neural cells, we also determined its localization in transfected CHO fibroblasts [6].
• In summary, VAChT differs in localization from the VMATs in PC12 cells but not CHO cells [6].

Chemical compound and disease context of Slc18a3

• Double immunostainings showed that cGMP-IR colocalized partial with the vesicular acetylcholine transporter molecule in lamina X, with Substance P in a subpopulation of neuronal fibers situated dorsolateral, and with a subpopulation of CGRP-IR dorsal root ganglion neurons [7].

Biological context of Slc18a3

• The human VAChT gene also localizes to chromosome 10 near the gene for choline acetyltransferase [8].
• Here, we show that the first intron of the rat ChAT gene contains an open reading frame that encodes a potential vesicular acetylcholine transporter based on the following criteria [9].
• The results demonstrate that analysis of microscopic kinetics is required for the correct interpretation of mutational effects in VAChT [10].
• Acetylcholine binding site in the vesicular acetylcholine transporter [10].
• 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 [1].

Anatomical context of Slc18a3

• The VAChT-labeled dendritic tubulovesicles often apposed unlabeled axon terminals that formed symmetric synapses [11].
• Membranes of tubulovesicles in other selective dendrites were also VAChT-labeled, and almost half of these dendrites displayed plasmalemmal MOR immunoreactivity [11].
• Vesicular acetylcholine transporter in the rat nucleus accumbens shell: subcellular distribution and association with mu-opioid receptors [11].
• The role of clathrin-associated protein complexes in VAChT sorting to synaptic vesicles has been examined [12].
• It is concluded that bipolar cortical GABA interneurons in certain rodent species may develop ChAT immunoreactivity but not VChAT immunoreactivity making the cholinergic relevance of ChAT in the GABA interneurons uncertain and may exclude these neurons from being part of the traditionally defined cholinergic system [13].

Associations of Slc18a3 with chemical compounds

• In neuronal cells the neurotransmitter acetylcholine is transferred from the cytoplasm into synaptic vesicles by the vesicular acetylcholine transporter (VAChT) [12].
• A classical tyrosine motif is also involved in VAChT trafficking, but does not interact with any known adaptor proteins [12].
• A fusion protein between the VAChT cytoplasmic tail and glutathione S-transferase was used to identify VAChT-clathrin-associated protein adaptor protein 1, adaptor protein 2 and adaptor protein 180 complexes from a rat brain extract [12].
• The observations suggest a model in which the known ion pair between lysine in TMD II and aspartate in TMD XI controls the conformation or relative position of TMD XI, which in turn controls additional TMDs in the C-terminal half of VAChT [14].
• Replacement of Ser-480 by glutamate, to mimic the phosphorylation event, increases the localization of VAChT to LDCVs [5].

Regulatory relationships of Slc18a3

• Double labeling of Fos with protein gene product 9.5 revealed the neuronal identity of activated cells that were encircled by varicose fibers immunoreactive to vesicular acetylcholine transporter [15].

Other interactions of Slc18a3

• Coregulation of two embedded gene products, choline acetyltransferase and the vesicular acetylcholine transporter [16].
• 5. The results suggest that in the rat CC, nNOS, VAChT- and VIP-immunoreactivities can be found in the same parasympathetic cholinergic neurons [17].
• VMAT2 and the vesicular acetylcholine transporter VAChT were co-expressed in early development of the primary sympathetic chain as well as in the cranial parasympathetic ganglia [18].
• 5-HT1A receptor immunoreactivity was also detected in a subpopulation of VAChT-containing cholinergic neurons of the MSDB [19].
• The cholinergic locus: ChAT and VAChT genes [20].

Analytical, diagnostic and therapeutic context of Slc18a3

• Deletion and site directed mutagenesis show that the VAChT cytoplasmic tail contains multiple trafficking signals [12].
• Neurotransmission system markers, including tyrosine hydroxylase, vesicular monoamine transporter, vesicular acetylcholine transporter and excitatory amino acid carrier1 were analyzed by immunohistochemistry [21].
• In PC12 cells, VAChT differs from the VMATs by immunofluorescence and fractionates almost exclusively to SLMVs and endosomes by equilibrium sedimentation [6].
• Subcellular localization of VAChT in specific organelles in neuronal cells was examined by immunoelectron microscopy in a rat neuronal cell line (PC 12-c4) expressing VAChT as well as the endocrine and neuronal forms of the vesicular monoamine transporters (VMAT1 and VMAT2) [22].
• These antibodies specifically recognized full-length recombinant VAChT expressed in transfected HeLa cells by Western blotting, with the prominent immunoreactive band at 55 kDa [23].

References