ライフサイエンスコーパス: VAChT

1 VAChT and the VMATs contain COOH-terminal, cytoplasmic d

2 VAChT and VMAT exchange two protons per substrate molecu

3 VAChT and VMAT exhibit partial structural and mechanisti

4 VAChT binding estimates varied by a factor of greater th

5 VAChT immunoreactivity was found exclusively within pres

6 VAChT immunoreactivity was in unmyelinated axons and axo

7 VAChT immunoreactivity was observed in the SCN, LSPV, an

8 VAChT is found in synaptic regions, whereas ChAT appears

9 VAChT(+) synapses onto DA and mesoaccumbens neurons were

10 VAChT(+) terminals were visualized by using diaminobenzi

11 VAChT-immunoreactive terminals apposed to Renshaw cells

12 VAChT-labeled presynaptic profiles were most concentrate

13 Nearly all (99% +/- 1%) VAChT-immunoreactive synapses expressed NRG1.

14 is similar to the interaction between UNC-17/VAChT and synaptobrevin.

15 identify proteins that interact with UNC-17/VAChT, we screened for mutations that suppress the uncoo

16 bit polyclonal antibodies, generated using a VAChT C-terminus/glutathione-S-transferase fusion protei

17 Additionally, VAChT-IR presynaptic profiles apposed ERalpha-IR dendrit

18 The antiserum against VAChT marked the inner epithelial layer.

19 ce between the number of ChAT- (210,000) and VAChT- (174, 000) immunopositive neurons in the nbM per

20 The presence of 5HT- and VAChT-immunoreactive cells in segments of the common car

21 ChAT and VAChT are found in the same neurons, including more than

22 he cholinergic locus containing the ChAT and VAChT genes.

23 The relative levels of Drosophila ChAT and VAChT mRNA differ, however, in different tissues or in C

24 7-, alpha3beta2-, and beta3-nAChRs, ChAT and VAChT pathways.

25 Although transcripts for ChAT and VAChT protein have been localized in cholinergic neurons

26 tor acting via the TrkA receptor on ChAT and VAChT proteins in contextual memory consolidation.

27 f hippocampal terminals labeled for ChAT and VAChT proteins.

28 ting that independent regulation of ChAT and VAChT transcripts may occur post-transcriptionally.

29 express the ACh-processing proteins ChAT and VAChT, and reducing their expression impairs learned olf

30 ic neurons, and the coexpression of ChAT and VAChT, are relatively preserved in early stages of AD.

31 common transcriptional control for ChAT and VAChT.

32 observed that nicotine upregulated ChAT and VAChT.

33 The number of ChAT- and VAChT-immunopositive neurons was shown to correlate sign

34 owed that a majority of PACAP-LI, VIP-LI and VAChT-LI nerve endings making putative synaptic contact

35 ctal myenteric ganglia, alpha-synuclein- and VAChT-immunoreactivity coexisted in 15 +/- 1.4% of bioti

36 complex between protonated [3H]vesamicol and VAChT decreases from 12 nM at neutral pH to 2.1 nM at pH

37 DbetaH expression, whereas VGLUT1, VGAT, and VAChT showed no change.

38 Both VMAT2 and VAChT thus use leucine-based signals for efficient endoc

39 OS-positive) and somatic motor neurons (anti-VAChT-positive).

40 All the somata in the PPG expressed both VAChT and nNOS immunoreactivity (IR).

41 ut not when visualized for quantification by VAChT immunoreactivity.

42 In CHO cells, VAChT localizes to the same endosomal compartment as the

43 In PC12 cells, VAChT differs from the VMATs by immunofluorescence and f

44 l-time PCR showed that mRNA levels for ChAT, VAChT, and alpha7 and beta2 nAChR subunits varied signif

45 T mRNA expression, while it upregulated ChAT/VAChT mRNA levels and ChAT activity.

46 n of alpha-synuclein-IR axons also contained VAChT immunoreactivity (78% +/- 1.3%, n = 4) compared wi

47 Cell bodies containing VAChT were not found at any site.

48 ction analysis indicates that all Drosophila VAChT specific transcripts contain the shared first exon

49 The predicted Drosophila VAChT protein is composed of 578 amino acids and contain

50 Before and during VAChT acquisition, the developing sweat gland innervatio

51 c neurons, little is known about the encoded VAChT protein.

52 on of CHT and ChAT, and, to a lesser extent, VAChT.

53 and tested, 6 display very high affinity for VAChT (K(i), 0.25-0.66 nM) and greater than 500-fold sel

54 19k, and 24a-b) displayed high affinity for VAChT (Ki = 0.93-18 nM for racemates) and moderate to hi

55 assessed by the immunostaining of fibers for VAChT (vesicular acetylcholine transporter).

56 ippocampal formation, immunoreactivities for VAChT and ERalpha both were presynaptic, although their

57 Compound (-)-[(11)C]24b (Ki = 0.78 nM for VAChT, 1200-fold over sigma receptors) was successfully

58 tetralin (9e) has K(i) values of 2.70 nM for VAChT, 191 nM for sigma(1), and 251 nM for sigma(2).

59 ts suggest a complex trafficking pathway for VAChT.

60 ed into the carbonyl-containing scaffold for VAChT ligands.

61 M) and greater than 500-fold selectivity for VAChT over sigma(1) and sigma(2) receptors.

62 emates) and moderate to high selectivity for VAChT over sigma1 and sigma2 receptors (Ki = 44-4400-fol

63 y (K(i), 1.0-10 nM) and good selectivity for VAChT.

64 10) display moderate to high selectivity for VAChT.

65 ribosome scanning model may not be used for VAChT translation initiation.

66 which leads to overexpression of functional VAChT and consequently increased cholinergic tone.

67 he vesicular acetylcholine transporter gene (VAChT), which leads to overexpression of functional VACh

68 (hereafter called [3H]vesamicol), and human VAChT expressed in PC12(A123.7) cells.

69 The transport of [3H]ACh by human VAChT was dependent upon the addition of exogenous ATP a

70 The kinetics of [3H]ACh uptake by human VAChT were saturable, exhibiting an apparent Km of 0.97

71 ent affinity (Kd) of [3H]vesamicol for human VAChT was 4.1 +/- 0.5 nM, and the Bmax was 8.9 +/- 0.6 p

72 e work reported here, E309 and D398 in human VAChT were mutated singly and together to test their fun

73 conserved amino acid residues found in human VAChT with the mutated residue in CeVAChT and stably exp

74 The human VAChT protein was abundantly expressed in this line and

75 The turnover (Vmax/Bmax) of the human VAChT was approximately 65/min.

76 of vesicular transporters so far identified (VAChT and VGAT) were first described and cloned in C. el

77 utathione S-transferase was used to identify VAChT-clathrin-associated protein adaptor protein 1, ada

78 ar acetylcholine transporter-immunoreactive (VAChT-IR) varicosities (80% +/- 1.7%, n = 4, P < 0.001)

79 In VAChT-positive perikarya, the immunogold particles were

80 ore classical neurotransmitters, a change in VAChT trafficking due to phosphorylation may also influe

81 ndicates that specific structural changes in VAChT translate into specific alterations in the intrins

82 of clathrin-associated protein complexes in VAChT sorting to synaptic vesicles has been examined.

83 ntional demand revealed striking deficits in VAChT-deleted mice.

84 rect interpretation of mutational effects in VAChT.

85 classical tyrosine motif is also involved in VAChT trafficking, but does not interact with any known

86 actate, suggesting altered PFC metabolism in VAChT-deficient mice.

87 M2R-ir was also seen in VAChT(+) cholinergic terminals, indicating a possible au

88 n present changes in alternative splicing in VAChT-deficient mice, including pyruvate kinase M, a key

89 new insights into the tertiary structure in VAChT.

90 These results suggest that increased VAChT expression may disrupt critical steps in informati

91 Interestingly, VAChT-targeted mice took longer to reach criteria in the

92 , SP-IR, and VIP-IR varicosities that lacked VAChT-immunoreactivity, only 1 +/- 0.3%, 0 +/- 0.3%, and

93 Full-length VAChT cDNA is 7.2 kilobase long and has unusually long 5

94 lionic axons within the ganglion showed less VAChT-immunoreactive intensity than that seen in the som

95 Loaded VAChT reorients quickly (73 000 min-1) and releases ACh

96 y with expression of the cholinergic marker, VAChT.

97 Mutated VAChTs were expressed in PC12(A123.7) cells and characte

98 immunological characterization of the native VAChT protein.

99 some markers are downregulated early (NeuN, VAChT, Chondrolectin) and others at end stage (Calca).

100 etrahydronaphthale ne (30b) (K(i) = 2.40 nM, VAChT/sigma selectivity index = 410) display moderate to

101 etrahydronaphth alene (28h) (K(i) = 0.66 nM, VAChT/sigma selectivity index = 294), and 5-amino-3-[4-(

102 -tetrahydronaphthalene (28b) (K(i) = 2.7 nM, VAChT/sigma selectivity index = 70), trans-3-[4-(5-iodot

103 ented toward the outside for nontransporting VAChT and toward the inside for transporting VAChT.

104 In the hilus and molecular layer, 4% of VAChT-ir terminals contacted dendritic shafts that were

105 uggest that phosphorylation of serine 480 of VAChT is involved in the trafficking of this transporter

106 Additionally, 7% of VAChT-ir presynaptic profiles directly apposed MOR-ir ax

107 71 +/- 0.8% of VAChT-IR varicosities in myenteric ganglia of human colo

108 that when mutated results in accumulation of VAChT at the plasma membrane.

109 dentical to the order of reduced affinity of VAChT for acetylcholine in vitro.

110 However, small amounts of VAChT also occur on LDCVs.

111 l of these mutants express normal amounts of VAChT protein and exhibit appropriate targeting of VAChT

112 seful for the structure/function analysis of VAChT.

113 ings, we directly compared the appearance of VAChT immunoreactivity in the sympathetic neurons that i

114 siRNA-mediated attenuation of VAChT reversed the apoptotic activity of vesamicol.

115 laxed (in contrast to tense) conformation of VAChT that binds vesamicol exceptionally tightly.

116 , thus eliminating potential denaturation of VAChT and failure of the filter assay.

117 es within the terminal cytoplasmic domain of VAChT, which specifically targets it to synaptic vesicle

118 Preexposure or long-term exposure of VAChT to high pH does not affect binding, thus eliminati

119 olinergic markers, whereas the expression of VAChT mRNA in the Ipc was undetectable in our essays.

120 However, the function of VAChT in the nucleus remains to be shown.

121 ls additional TMDs in the C-terminal half of VAChT.

122 canning approaches provide a robust index of VAChT binding.

123 ion with vesamicol, a selective inhibitor of VAChT, and displays vesamicol-insensitive uptake of acet

124 Vesamicol, an inhibitor of VAChT, and hemicholinium-3, an inhibitor of choline tran

125 vealed a 36% increase in the total length of VAChT-positive cholinergic fibers in the IML after EC da

126 accompanied by an increase in the levels of VAChT, the vesicular transporter for ACh, and confirm th

127 ut little change or even increased levels of VAChT.

128 ylation event, increases the localization of VAChT to LDCVs.

129 5% to 13% (depending on laminar location) of VAChT-immunoreactive (ir) presynaptic profiles contained

130 The simplest model of VAChT that explains the behavior requires a proton at si

131 odel than an alternative hydropathy model of VAChT that likely locates E309 far from D398 and the ACh

132 the performance of control mice, but not of VAChT-deficient mice on the 5-CSRT.

133 e exhibited a significantly higher number of VAChT profiles than in control fish.

134 AI (E(2)+AI) rescued a significant number of VAChT stained nerve endings and treatment of fish with E

135 wo species, but similar temporal patterns of VAChT expression were found across species.

136 esults of this study confirm the presence of VAChT in cutaneous nerves and in both epidermal melanocy

137 About three-quarters of VAChT+ cholinergic terminals formed synapses; the main p

138 The cytoplasmic tail of VAChT has been shown to contain signals that direct its

139 protein and exhibit appropriate targeting of VAChT to synaptic vesicles.

140 In tissue labeled for GABA, one-third of VAChT(+) terminals innervated GABA-labeled dendrites, in

141 s it was found outside of the active zone of VAChT+ synapses.

142 MBON activation depends on VAChT expression in Kenyon cells and is blocked by ACh r

143 Because E309Q has no effect on VAChT functions at physiological pH, E309 has no apparen

144 Cells containing either 5HT or VAChT were found in all three sites.

145 generated antibodies that recognize ChAT or VAChT in a model organism, the nematode Caenorhabditis e

146 in stable PC12 transformants overexpressing VAChT.

147 Early downregulation of presynaptic VAChT and Chrna2 was correlated with disconnection from

148 vesicular acetylcholine transporter protein (VAChT), a marker for cholinergic axons, was performed to

149 nyl and piperidyl groups of the prototypical VAChT ligand vesamicol and its more potent analogues ben

150 for the physiological function of a putative VAChT and demonstrate that quantal size can be regulated

151 Rat VAChT has a number of aspartate residues within its pred

152 Rat VAChT in wild-type and mutant forms was expressed in PC1

153 s over levels attained by the endogenous rat VAChT, expressed at low levels in control PC-12 cells.

154 g Xenopus spinal neurons by injection of rat VAChT cDNA or synthetic mRNA into Xenopus embryos.

155 putative transmembrane domains (TMDs) of rat VAChT was mutated to A and a different aromatic residue

156 g a permanently dephosphorylated form of rat VAChT, S480A rVAChT, it was shown that this mutant displ

157 tested in the paper reported here using rat VAChT expressed in PC12(A1237) cells.

158 cifically recognized full-length recombinant VAChT expressed in transfected HeLa cells by Western blo

159 In rat brain homogenates, a single VAChT-immunoreactive band of approximately 70 kDa was pr

160 a(Ast)(+/+) mice) leads to very low skeletal VAChT expression and ACh levels.

161 In summary, VAChT differs in localization from the VMATs in PC12 cel

162 e (VGLUT1-positive) and motor axon synapses (VAChT-positive) initially target several different V1 in

163 In the pairwise test, VAChT-deficient mice were able to learn, but were impair

164 In tissue labeled for TH, VAChT(+) terminals frequently synapsed onto DA mesoaccum

165 distributed between hippocampal lamina than VAChT-IR profiles.

166 als apposed to motoneurones, but larger than VAChT-immunoreactive terminals contacting other ventral

167 These findings confirm that VAChT protein is expressed uniquely in cholinergic neuro

168 Therefore, we conjectured that VAChT antagonists, such as vesamicol, may suppress the g

169 We find that VAChT immunoreactivity is not detectable in either the a

170 We propose that VAChT-targeted mice can be used to model and to dissect

171 quires target interactions and revealed that VAChT does not appear in the absence of glands.

172 roscopy using immunoperoxidase revealed that VAChT was localized in axon terminals, and using more pr

173 ative ultrastructural analysis revealed that VAChT-IR presynaptic profiles contained ERalpha immunore

174 We now show that VAChT undergoes regulated phosphorylation by protein kin

175 Since previous work has suggested that VAChT expression confers little if any transport activit

176 The VAChT di-leucine sequence also confers internalization w

177 A fusion protein between the VAChT cytoplasmic tail and glutathione S-transferase was

178 consistent with in vivo selectivity for the VAChT with an initial uptake of 0.911 %ID/g in rat stria

179 to serve as PET/SPECT probes for imaging the VAChT in vivo.

180 These features of the VAChT 5'-UTR region suggest that a ribosome scanning mod

181 Comparative analysis of the VAChT and VMAT transport mechanisms will aid understandi

182 a common first exon and the remainder of the VAChT gene contains a single coding exon residing entire

183 that map to highly conserved regions of the VAChT gene of Caenorhabditis elegans (CeVAChT) (unc-17)

184 Most of the VAChT-positive fibers and some of the TH-positive nerves

185 en vesamicol and ACh in over one-half of the VAChT.

186 be a PET tracer for clinical imaging of the VAChT.

187 n characterizing effects of mutations on the VAChT transport cycle.

188 and site directed mutagenesis show that the VAChT cytoplasmic tail contains multiple trafficking sig

189 Thus, VAChT differs in localization from the VMATs, which sort

190 ons and [3H]vesamicol compete for binding to VAChT.

191 -FEOBV PET confirms that the tracer binds to VAChT with the expected in vivo human brain distribution

192 Other phenomena related to VAChT, namely the time required to fill synaptic vesicle

193 alculation of a (123)I-iodobenzovesamicol-to-VAChT binding parameter, the nondisplaceable binding pot

194 against vesicular acetylcholine transferase (VAChT).

195 n of the vesicular acetycholine transporter (VAChT).

196 led for vesicular acetylcholine transporter (VAChT) and ERalpha and examined by electron microscopy.

197 for the vesicular acetylcholine transporter (VAChT) and for tyrosine hydroxylase (TH) and GABA.

198 to the vesicular acetylcholine transporter (VAChT) and has been used in preclinical studies to quant

199 led for vesicular acetylcholine transporter (VAChT) and MOR-1 and examined by electron microscopy.

200 rry the vesicular acetylcholine transporter (VAChT) and synaptic vesicle markers such as synaptophysi

201 (ChAT), vesicular acetylcholine transporter (VAChT) and the high-affinity choline transporter (CHT).

202 of the vesicular acetylcholine transporter (VAChT) and the neuronal vesicular monoamine transporter

203 for the vesicular acetylcholine transporter (VAChT) and used to assess the integrity of cholinergic p

204 related vesicular acetylcholine transporter (VAChT) and vesicular monoamine transporter (VMAT) transp

205 e human vesicular acetylcholine transporter (VAChT) cDNA are described.

206 related vesicular acetylcholine transporter (VAChT) contains a similar di-leucine sequence within the

207 AT) and vesicular acetylcholine transporter (VAChT) immunohistochemistry.

208 tin and vesicular acetylcholine transporter (VAChT) immunoreactivity and acetylcholinesterase histoch

209 des the vesicular acetylcholine transporter (VAChT) in Caenorhabditis elegans.

210 ing the vesicular acetylcholine transporter (VAChT) in the mouse forebrain.

211 of the vesicular acetylcholine transporter (VAChT) in the SCN, LSPV, and in two control areas.

212 Vesicular acetylcholine transporter (VAChT) is inhibited by (-)-vesamicol [(-)-trans-2-(4-phe

213 The vesicular acetylcholine transporter (VAChT) is responsible for the transport of the neurotran

214 ls, the vesicular acetylcholine transporter (VAChT) localizes preferentially to synaptic-like microve

215 The vesicular acetylcholine transporter (VAChT) mediates ACh storage in synaptic vesicles by exch

216 and the vesicular acetylcholine transporter (VAChT) revealed that PACAP is found in nerve terminals a

217 ence of vesicular acetylcholine transporter (VAChT) staining in the primary motor neurons as a result

218 zes the vesicular acetylcholine transporter (VAChT) suggest, however, that the development of choline

219 T), and vesicular acetylcholine transporter (VAChT) to determine whether Pb exposure alters the gluta

220 ing the vesicular acetylcholine transporter (VAChT) was also studied.

221 utative vesicular acetylcholine transporter (VAChT) was overexpressed in developing Xenopus spinal ne

222 The vesicular acetylcholine transporter (VAChT) was used as a marker for cholinergic terminals; c

223 and the vesicular acetylcholine transporter (VAChT) was used to examine the expression of these linke

224 ant rat vesicular acetylcholine transporter (VAChT) with radiolabeled inorganic phosphate was used to

225 ity for vesicular acetylcholine transporter (VAChT), a heteroaromatic ring or a phenyl group was intr

226 rs: the vesicular acetylcholine transporter (VAChT), the high-affinity choline transporter (CHT1) and

227 of the vesicular acetylcholine transporter (VAChT), we have interposed a carbonyl group between the

228 AT) and vesicular acetylcholine transporter (VAChT), which are critical for synthesis and storage of

229 ly more vesicular acetylcholine transporter (VAChT)-IR varicosities (88 +/- 3%, P < 0.001).

230 pecific vesicular acetylcholine transporter (VAChT).

231 MDs) of vesicular acetylcholine transporter (VAChT).

232 by the vesicular acetylcholine transporter (VAChT).

233 in the vesicular acetylcholine transporter (VAChT).

234 by the vesicular acetylcholine transporter (VAChT).

235 for the vesicular acetylcholine transporter (VAChT).

236 utative vesicular acetylcholine transporter (VAChT).

237 LC5A7), vesicular acetylcholine transporter (VAChT, SLC18A3), and nACh receptors (AChRs, CHRNAs).

238 odel of vesicular acetylcholine transporter (VAChT, TC 2.A.1.2.13).

239 lcholine (ACh) by vesicular ACh transporter (VAChT) is driven by a proton-motive force established by

240 se (ChAT) and the vesicular ACh transporter (VAChT), as well as alpha3, alpha5, alpha7, beta2, and be

241 ne (ACh), and the vesicular ACh transporter (VAChT), the synaptic vesicle membrane protein which pump

242 e closely related vesicular ACh transporter (VAChT).

243 r the PSNS marker vesicular ACh transporter (VAChT).

244 (vesicular acetylcholine (ACh) transporter (VAChT)) for both choline and ACh has never been shown in

245 uN and vesicular acethylcholine transporter [VAChT]), and two markers for fast motor neurons (Chondro

246 cells (vesicular acetylcholine transporter [VAChT]), tyrosine hydroxylase (TH), and serotonin (5HT)

247 cells (vesicular acetylcholine transporter [VAChT]), tyrosine hydroxylase (TH; the rate-limiting enz

248 ith the vesicular acetylcholine transporter; VAChT).

249 VAChT and toward the inside for transporting VAChT.

250 centrifugation showed that, unlike wild type VAChT, the S480A mutant did not localize to synaptic ves

251 Unlike wild-type VAChT, which exhibits a peak of [(3)H]vesamicol binding

252 Many nerve fibers were VAChT immunoreactive and a small number of fibers were T

253 umed excitatory) morphological type, whereas VAChT(+) synapses onto GABA cells were more frequently s

254 t glands was undertaken to determine whether VAChT expression requires target interactions and reveal

255 e 2 binds a proton (pKa2 = 7.0), after which VAChT reorients (150 +/- 20 min-1) in the rate-limiting

256 Similarly, in vivo studies with VAChT ligands suggest that the latter are potentially us

257 ned alpha-synuclein-immunoreactivity without VAChT-immunoreactivity.