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 expression was significantly reduced in the striat

6 VAChT immunoreactivity was found exclusively within pres

7 VAChT immunoreactivity was in unmyelinated axons and axo

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

9 VAChT is found in synaptic regions, whereas ChAT appears

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

11 VAChT(+) terminals were visualized by using diaminobenzi

12 VAChT-immunoreactive terminals apposed to Renshaw cells

13 VAChT-labeled presynaptic profiles were most concentrate

14 significantly reduced thalamic (p = 0.0016) VAChT expression in fallers compared to nonfallers.

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

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

17 at define cholinergic identity (e.g., unc-17/VAChT, cho-1/ChT).

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

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

20 In vivo injection of vesamicol-a VAChT blocker-at the cholinergic synapse, suppressed for

21 ss vesicular transporters for acetylcholine (VAChT) and glutamate (VGLUT3) and use acetylcholine/glut

22 D(2), dopamine transporter), acetylcholine (VAChT, M(1)), gamma-aminobutyric acid A (GABA(A)), and g

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

24 The antiserum against VAChT marked the inner epithelial layer.

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

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

27 D subjects underwent clinical assessment and VAChT ([(18) F]FEOBV) PET.

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

29 he cholinergic locus containing the ChAT and VAChT genes.

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

31 7-, alpha3beta2-, and beta3-nAChRs, ChAT and VAChT pathways.

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

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

34 f hippocampal terminals labeled for ChAT and VAChT proteins.

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

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

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

38 common transcriptional control for ChAT and VAChT.

39 observed that nicotine upregulated ChAT and VAChT.

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

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

42 orrelated with plasminogen, neuroserpin, and VAChT while NGF correlated with MMP9 activity.

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

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

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

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

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

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

49 ut not when visualized for quantification by VAChT immunoreactivity.

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

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

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

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

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

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

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

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

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

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

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

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

62 19k, and 24a-b) displayed high affinity for VAChT (Ki = 0.93-18 nM for racemates) and moderate to hi

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

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

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

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

67 ts suggest a complex trafficking pathway for VAChT.

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

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

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

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

72 10) display moderate to high selectivity for VAChT.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

87 In VAChT-positive perikarya, the immunogold particles were

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

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

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

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

92 rect interpretation of mutational effects in VAChT.

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

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

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

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

97 new insights into the tertiary structure in VAChT.

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

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

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

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

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

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

104 lst lowering their affinity to the mammalian VAChT 10-fold.

105 confirmed the presence of cholinergic marker VAChT (vesicular acetylcholine transporter) in the regio

106 y with expression of the cholinergic marker, VAChT.

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

108 immunological characterization of the native VAChT protein.

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

110 Neuronal VAChT staining and airway narrowing in response to elect

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

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

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

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

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

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

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

118 71 +/- 0.8% of VAChT-IR varicosities in myenteric ganglia of human colo

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

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

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

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

123 seful for the structure/function analysis of VAChT.

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

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

126 rrelated with the molecular concentration of VAChT, measured by [(18)F]fluoroethoxy-benzovesamicol (F

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

128 Specific deletion of VAChT in the dorsomedial striatum of adult mice was suff

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

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

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

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

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

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

135 canning approaches provide a robust index of VAChT binding.

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

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

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

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

140 ut little change or even increased levels of VAChT.

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

142 5% to 13% (depending on laminar location) of VAChT-immunoreactive (ir) presynaptic profiles contained

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

159 in stable PC12 transformants overexpressing VAChT.

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

161 Freezers had prominent VAChT expression reductions in the bilateral striatum, t

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

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

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

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

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

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

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

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

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

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

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

173 FoG status is associated with reduced VAChT expression in striatal cholinergic interneurons an

174 We examined associations between regional VAChT expression and freezing of gait (FoG) and falls.

175 Using mice with genetically silenced VAChT (VAChT conditional KO, VAChTcKO) or VGLUT3 (VGLUT3

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

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

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

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

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

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

182 distributed between hippocampal lamina than VAChT-IR profiles.

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

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

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

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

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

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

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

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

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

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

193 The VAChT di-leucine sequence also confers internalization w

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

211 against vesicular acetylcholine transferase (VAChT).

212 n of the vesicular acetycholine transporter (VAChT).

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

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

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

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

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

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

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

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

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

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

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

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

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

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

227 AT) and vesicular acetylcholine transporter (VAChT) in specific neural cells in the Ixodes synganglio

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

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

230 ist and vesicular acetylcholine transporter (VAChT) inhibitor analogues through bioisosteric replacem

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

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

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

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

235 Vesicular acetylcholine transporter (VAChT) PET ligands are better suited for evaluation of h

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

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

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

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

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

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

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

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

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

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

246 its the vesicular acetylcholine transporter (VAChT), a target recognized by commercial animal and cro

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

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

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

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

251 marker vesicular acetylcholine transporter (VAChT).

252 pecific vesicular acetylcholine transporter (VAChT).

253 MDs) of vesicular acetylcholine transporter (VAChT).

254 by the vesicular acetylcholine transporter (VAChT).

255 in the vesicular acetylcholine transporter (VAChT).

256 by the vesicular acetylcholine transporter (VAChT).

257 for the vesicular acetylcholine transporter (VAChT).

258 utative vesicular acetylcholine transporter (VAChT).

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

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

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

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

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

264 e closely related vesicular ACh transporter (VAChT).

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

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

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

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

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

270 ith the vesicular acetylcholine transporter; VAChT).

271 naptic vesicular acetylcholine transporters (VAChT), (-)-(18)F-fluoroethoxybenzovesamicol ((18)F-FEOB

272 VAChT and toward the inside for transporting VAChT.

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

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

275 Using mice with genetically silenced VAChT (VAChT conditional KO, VAChTcKO) or VGLUT3 (VGLUT3cKO), w

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

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

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

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

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

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