High impact information on Slc18a3

• VAChT deficiency alters synaptic vesicle filling and affects ACh release [1].
• An important step for cholinergic transmission involves the vesicular storage of acetylcholine (ACh), a process mediated by the vesicular acetylcholine transporter (VAChT) [1].
• These observations suggest a critical role of VAChT in the regulation of ACh release and physiological functions in the peripheral and central nervous system [1].
• The decrease of VAChT in the patient samples studied is restricted to the striatum and does not occur in the hippocampus or the spinal cord [2].
• Excitatory motor neurons, labeled with antibodies to vesicular acetylcholine transporter or substance-P, were closely associated with IC-IM [3].

Biological context of Slc18a3

• Transfection assays showed that this region strongly represses the activity of the native VAChT promoters in non-neuronal cells, but has no major effect in neuronal cells whether or not they express the endogenous ChAT and VAChT genes [4].
• Moreover, we found that clathrin-mediated endocytosis of VAChT is required for targeting to microvesicles in SN56 and PC12 cells [5].

Anatomical context of Slc18a3

• Within the sensory epithelium, TH-positive terminals are seen only in the inner hair cell area, where they intermingle with other olivocochlear terminals expressing cholinergic markers (vesicular acetylcholine transporter; VAT) [6].
• In mice homozygous for a mutational inactivation of the transcription factor Phox2b, ChAT and VAChT mRNA expression is absent from sympathetic ganglia [7].
• Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed expression of mouse VAChT mRNA in spinal cord, brain (excluding the cerebellum) and brain stem, but not in peripheral tissues such as liver and kidney [8].
• The size of the basal forebrain cholinergic neurons and the pattern of cholinergic synapses in the hippocampus and cerebral cortex were revealed by immunohistochemical staining for choline acetyltransferase and the vesicular acetylcholine transporter, respectively [9].
• Double in situ hybridization histochemistry for vesicular acetylcholine transporter identified VGLUT3 neurons in the striatum as cholinergic interneurons, whereas VGLUT3 mRNA and protein were absent from all other cholinergic cell groups [10].

Associations of Slc18a3 with chemical compounds

• Dibutyryl cAMP had a greater effect on the level of VAChT mRNA (4-fold induction) than on the level of ChAT mRNA (2-fold induction), suggesting a quantitatively differential transcriptional regulation of the two genes by the cAMP pathway [11].
• All-trans-retinoic acid increased both ChAT and VAChT mRNA levels in SN56 cells up to 3.5-fold, and elevated intracellular ACh levels by 2.5-fold [11].
• The vesicular acetylcholine transporter (VAChT) regulates the amount of acetylcholine stored in synaptic vesicles [5].
• Deletion and alanine-scanning mutants lacking most of the carboxyl tail of VAChT, but containing residues 481-490, were still targeted to microvesicles [5].
• Dexamethasone up-regulated ChAT and VAChT in SN56 cells, while it had inhibitory effects on these genes in PC12 cells [12].

Other interactions of Slc18a3

• Already at embryonic day 16 (E16), ChAT and VAChT-positive cells are affected by the c-ret mutation [13].
• Periosteal innervation of mice lacking CNTF, LIF, or both, like that of wild-type mice, is immunoreactive for the vesicular acetylcholine transporter, a recently identified cholinergic marker, and VIP [14].
• The distribution of calcitonin gene-related peptide (CGRP)-, nNOS-, VAChT- and VIP-IR nerve structures was unchanged [15].
• Synaptophysin-, VAChT- and NOS-immunoreactive nerve terminals were present within the external muscle prior to the formation of receptor clusters, and their appearance did not follow any apparent rostrocaudal sequence [16].
• VAChT-positive preganglionic neurons were found to terminate on ZnT3 neuronal somata [17].

Analytical, diagnostic and therapeutic context of Slc18a3

• Here, we use site-directed mutagenesis to evaluate the contribution of the C-terminal tail of VAChT to the targeting of this transporter to synaptic-like microvesicles in cholinergic SN56 cells [5].
• Immunohistochemistry confirmed that nerves immunoreactive for nitric oxide synthase, vesicular acetylcholine transporter and vasoactive intestinal polypeptide were substantially reduced in cavernosum of NTN knockout mice [18].
• Immunohistochemistry and confocal laser microscopy, using the goat VAChT antisera, showed strong immunoreactivity in discrete fibers and neuronal cell bodies of the central and peripheral nervous systems [19].
• Samples were fixed in 4% paraformaldehyde and processed for immunofluorescence histochemistry for cGMP, neuronal NO synthase (nNOS), vesicular acetylcholine transferase (VAChT), calcitonin gene-related polypeptide (CGRP) and protein gene product (PGP) 9 [20].

References