ライフサイエンスコーパス: syntaxin 1

1 F4/80, choline acetyltransferase (ChAT), and syntaxin 1.

2 finger protein, Staring, that interacts with syntaxin 1.

3 tion and proteasome-dependent degradation of syntaxin 1.

4 II-mediated phosphorylation on serine-14 of syntaxin 1.

5 he Mint.Munc18-1 complex in conjunction with syntaxin 1.

6 re greatly enriched, instead, in SNAP-25 and syntaxin 1.

7 binds to the first 80 N-terminal residues of syntaxin-1.

8 s a more than 10-fold excess of SNAP-25 over syntaxin-1.

9 ve the same cavity of Munc18-1 that binds to syntaxin-1.

10 roteins can co-reside on membrane-integrated syntaxin-1.

11 1 binding to SNARE complexes containing open syntaxin-1.

12 ation and to SNARE complexes containing open syntaxin-1.

13 eptin 5 by Cdk5/p35 decreases its binding to syntaxin-1.

14 attachment protein receptor (SNARE) protein Syntaxin-1.

15 htly to assembled SNARE complexes containing syntaxin-1.

16 e kinesin family member 5B (KIF5B) motor and syntaxin-1.

17 ts SNARE complex formation by absorbing free syntaxin-1.

18 synapses via lateral diffusion together with syntaxin-1.

19 l 69 residues are crucial for the binding to syntaxin-1.

20 unc18-1 binding to the N-terminal peptide of syntaxin-1.

21 corresponding C-terminal region can bind to syntaxin-1.

22 Syntaxin 1, 3, and 5 could not be detected.

23 Syntaxins 1-4 are localized to the plasma membrane, and

24 and 18c) bind to the closed conformation of syntaxins 1-4, which requires the N-terminal H(abc) doma

25 Most taste cells expressing syntaxin-1 (82%) also expressed the A blood group antige

26 of a core synaptic fusion complex containing syntaxin-1 A, synaptobrevin-II and SNAP-25B.

27 on the membrane of a vesicular carrier, and syntaxin 1, a SNARE on the target membrane, as well as t

28 Recently, it was shown that PI(4,5)P2and syntaxin 1, a SNARE protein that catalyzes regulated exo

29 Syntaxin-1, a core protein of the soluble N-ethylmaleimi

30 Similar to Munc13-1, CAPS1 binds to syntaxin-1, a key t-SNARE protein in neurosecretion.

31 amino terminus of Abi-1 that interacts with Syntaxin-1, a SNARE family member.

32 We observed that endogenous syntaxin-1 accumulates at the Golgi of Munc18-1 KO neuro

33 c-18 mutants, UNC-64 (Caenorhabditis elegans Syntaxin-1) accumulates in neuronal cell bodies.

34 attachment protein receptor (SNARE) protein syntaxin-1 adopts a closed conformation when bound to Mu

35 lates fusion both as a fusion restraint that syntaxin-1 alleviates and as an essential cofactor that

36 We conclude that clustering of syntaxin-1 allows the cell to maintain a high syntaxin-1

37 s in two distinct modes (i.e., with isolated syntaxin-1 alone in a "closed" conformation and with ass

38 Syntaxin 1, an essential protein in synaptic membrane fu

39 om brain extracts that predominantly contain syntaxin 1 and 2.

40 the inner plexiform layer strata displaying syntaxin 1 and ChAT.

41 hed E2 ubiquitin-conjugating enzyme UbcH8 to syntaxin 1 and facilitates the ubiquitination and protea

42 -1 is a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytos

43 brane protein 2) on the synaptic vesicle and syntaxin 1 and SNAP-25 (synaptosome-associated protein o

44 We demonstrate that syntaxin 1 and SNAP-25 cooperate as SNARE proteins to su

45 lso contained the synaptic t-SNARE proteins, syntaxin 1 and SNAP-25, suggesting that SV2B may partici

46 Focusing on syntaxin 1 and SNAP-25, we implemented direct stochastic

47 -embedded t-SNAREs consisting of full-length syntaxin 1 and SNAP-25B at the membrane, as measured by

48 The expression of syntaxin 1 and synaptosome-associated protein of 25 kDa

49 shes the ability of SNAP-25 to interact with syntaxin 1 and VAMP2 and prevents the assembly of the SN

50 d protein of 25 kDa (SNAP-25) interacts with syntaxin 1 and vesicle-associated membrane protein 2 (VA

51 fied as a molecular clamp that controls free syntaxin-1 and dynamin-1 availability and thereby regula

52 3a of Munc18-1 abolishes its ability to bind syntaxin-1 and fails to rescue the level and trafficking

53 aphilin competes with SNAP-25 for binding to syntaxin-1 and inhibits SNARE complex formation by absor

54 quires the polybasic juxtamembrane region of syntaxin-1 and is not affected by the superclamp mutatio

55 thereby increasing the immunoavailability of syntaxin-1 and leading indirectly to Ca(2+) current inhi

56 rprisingly, we find that both lipid-anchored syntaxin-1 and lipid-anchored synaptobrevin-2 lacking TM

57 Although SNARE complexes containing open syntaxin-1 and Munc18-1 are essential for exocytosis, th

58 Syntaxin-1 and Munc18-1 depend on each other for normal

59 H+-ATPase binds directly to the H3 domain of syntaxin-1 and not through VAMP-2 or SNAP-23.

60 mutant of P335A reduces the ability to bind syntaxin-1 and rescue syntaxin-1 levels.

61 ronal SM protein Munc18-1 and SNARE proteins syntaxin-1 and SNAP-25 (25 kDa synaptosome-associated pr

62 that CAPS exhibits high affinity binding to syntaxin-1 and SNAP-25 and moderate affinity binding to

63 synaptobrevin and the plasma membrane SNAREs syntaxin-1 and SNAP-25 assemble into a tight SNARE compl

64 ibody targeting otoferlin immunoprecipitated syntaxin-1 and SNAP-25 but not synaptobrevin-1.

65 ctor (NSF) and alpha-SNAP, which disassemble syntaxin-1 and SNAP-25 heterodimers.

66 ype SNAP-25, indicating that pairing between syntaxin-1 and SNAP-25 is required for parietal cell act

67 ngle molecules, and the numbers of unlabeled syntaxin-1 and SNAP-25 molecules per cell.

68 Fifty to seventy copies each of syntaxin-1 and SNAP-25 molecules were associated with a

69 we observed nanoscale clusters consisting of syntaxin-1 and SNAP-25 that contained associated Munc18-

70 ly, VAMP4 forms a stable complex with SNAREs syntaxin-1 and SNAP-25 that does not interact with compl

71 Its components, syntaxin-1 and SNAP25, are largely present in individual

72 tially containing the plasma membrane SNAREs syntaxin-1 and soluble NSF attachment protein (SNAP)-25.

73 tion of the synaptic SNARE proteins SNAP-25, syntaxin-1 and synaptobrevin-2, as well as by an age-dep

74 o exocytosis, they must recruit the proteins syntaxin-1 and synaptosomal associated protein 25 (SNAP-

75 unc18-1 with the N-terminal H(abc) domain of syntaxin-1 and the four-helical bundle of the assembled

76 bility of the Munc18-1 variants to chaperone syntaxin-1 and to rescue exocytosis is strongly impaired

77 The neuronal SM protein Munc18-1 binds to syntaxin-1 and to the SNARE complex through interactions

78 ays a significant role in the chaperoning of syntaxin-1 and, if so, how these dual functions of domai

79 racts from brain regions shows that SNAP-25, syntaxin 1, and 4 are broadly distributed, while SNAP-23

80 CAPS bound syntaxin-1, and CAPS truncations that competitively inhi

81 N-peptide is not spatially constrained along syntaxin-1, and it is functional when translocated to an

82 quires Munc18-1, which binds to the released syntaxin-1, and Munc13-1, which, together with Munc18-1,

83 rans complexes of the SNARE proteins VAMP-2, syntaxin-1, and SNAP-25 that bridge vesicle and plasma m

84 The presence of complexin I/II, syntaxin-1, and synapsin I in rabbit horizontal cell pro

85 subcellular distribution of complexin I/II, syntaxin-1, and synapsin I in rabbit retina.

86 ly of the SNARE complex composed of SNAP-25, syntaxin-1, and synaptobrevin-2 (sybII) proteins.

87 ermolecular interactions among the receptor, syntaxin-1, and the Ca(V)2.2 channel.

88 Syntaxin-1 appeared only in taste cells, but SNAP-25, sy

89 fails to rescue the level and trafficking of syntaxin-1 as well as to restore exocytosis in Munc18-1/

90 that DAP kinase binds to and phosphorylates syntaxin-1 at serine 188.

91 tion as a molecular clamp that controls free syntaxin-1 availability for the assembly of the SNARE co

92 Pre-docked syntaxin 1-based SNARE complexes bound by Munc18-1 were

93 is trafficking defect is specific for UNC-64 Syntaxin-1, because 14 other SNARE proteins and two acti

94 APS truncations that competitively inhibited syntaxin-1 binding also inhibited CAPS-dependent fusion.

95 he Sly1 N-terminal domain is opposite to the syntaxin 1-binding surface of the Munc18-1 N-terminal do

96 AMP-2 and SNAP-23, but only non-H3-truncated syntaxin-1 bound H+-ATPase, and synt-1ADeltaC expression

97 nt liposome fusion with N-terminal truncated syntaxin-1 but exhibits impaired activity with C-termina

98 nc18-1 that preserve tight binding to closed syntaxin-1 but markedly disrupt Munc18-1 binding to SNAR

99 s known to bind tightly to the SNARE protein syntaxin-1, but only when syntaxin-1 is in a closed conf

100 Munc18-1 reclustering was independent of syntaxin-1, but required calcium influx and protein kina

101 Here we report that cleavage of syntaxin 1 by BoNT/C, and cleavage of SNAP-25 by BoNT/E

102 and its binding partner, the t-SNARE-protein Syntaxin-1, by approximately 30% and decrease spontaneou

103 at the preferential binding of CAPS1 to open syntaxin-1 can contribute to the stabilization of the op

104 As expected for a C-terminal binding site on syntaxin-1, CAPS stimulates SNARE-dependent liposome fus

105 alpha-helix containing Pro-335 promotes the syntaxin-1 chaperoning function, whereas the P335A mutat

106 ion could not be explained by differences in syntaxin-1 chaperoning/localization or vesicle docking,

107 l cholesterol depletion, leading directly to syntaxin-1 cluster dispersal and Ca(2+) current inhibiti

108 Also, calcium was shown to promote syntaxin 1 clustering in the plasma membrane, but the mo

109 te Ca(2+) influx by expanding or contracting syntaxin-1 clusters.

110 1-226 bound poorly in vitro with recombinant syntaxin-1 compared with wild type SNAP-25, indicating t

111 Correspondingly, the N-terminal region of syntaxin-1 competes with the SNARE four-helix bundle and

112 1 catalyzes the transition from the Munc18-1/syntaxin-1 complex to the SNARE complex, the molecular m

113 s this fusion, in part by forming the closed syntaxin-1 conformation.

114 The synaptic target membrane SNARE syntaxin 1 contains a highly conserved H(abc) domain, wh

115 et of Munc18-1 rescues impaired secretion in syntaxin-1-depleted PC12 cells and the lethality and let

116 The C-terminal site for CAPS binding on syntaxin-1 does not overlap the Munc18-1 binding site an

117 Thus, the N-terminal syntaxin-1 domains mediate different functions in synapt

118 ailable about the in vivo functions of these syntaxin-1 domains.

119 te to the stabilization of the open state of syntaxin-1 during its transition from "closed" state to

120 -attachment protein receptor (SNARE) protein syntaxin-1 exhibits two conformations that both bind to

121 smitter release machinery, and regulation of syntaxin 1 expression levels is thought to contribute to

122 yntaxin-1 allows the cell to maintain a high syntaxin-1 expression level without compromising Ca(2+)

123 Munc18-1 binds to the SNARE syntaxin-1 folded into a closed conformation and to SNAR

124 8-1, which binds to the SNARE complex and to syntaxin-1 folded into a closed conformation.

125 Exocytosis likely starts with Syntaxin-1 folded into a self-inhibited closed conformat

126 vel E3 ubiquitin-protein ligase that targets syntaxin 1 for degradation by the ubiquitin-proteasome p

127 napses use classical SNARE machinery such as syntaxin-1 for neurotransmitter release in rat circumval

128 mpromising Ca(2+) influx, and recruitment of syntaxin-1 from clusters by SNAP-25 expression makes it

129 ous or exogenous SNAP-25 expression recruits syntaxin-1 from clusters on the plasma membrane, thereby

130 Thus, the closed conformation of syntaxin-1 gates the initiation of the synaptic vesicle

131 ptide is functionally important, whereas the syntaxin-1 H(abc)-domain is not, but limited information

132 Lim-syn isoforms showed great identity with syntaxin 1-homologs (syntaxin 1A/1B) from various other

133 g and trafficking the central SNARE protein, syntaxin-1 (i.e. chaperoning function), by its domain-1;

134 inding protein Doc2B or ubMunc13-2 increases syntaxin-1 immunoavailability and concomitantly down-reg

135 racted with ER and Golgi syntaxin 5 and with syntaxin 1 in the absence of Munc18a, when syntaxin 1 is

136 its biochemical interaction with the t-SNARE syntaxin-1 in a closed conformation caused premature ter

137 However, whether CAPS1 interacts with syntaxin-1 in a similar mode to Munc13-1 remains unclear

138 nd with assembled SNARE complexes containing syntaxin-1 in an "open" conformation).

139 yntaphilin and inhibits its interaction with syntaxin-1 in neurons.

140 vestigated the presynaptic membrane protein, syntaxin-1, in circumvallate taste buds of the rat.

141 basic residues in the plasma membrane SNARE syntaxin-1 increase inhibition by PI 4,5-P(2), suggestin

142 In contrast, syntaxin-1 inhibits Ca(2+) currents independently of SNA

143 Syntaxin 1 is a SNARE protein that plays a central role

144 Syntaxin 1 is an essential component of the neurotransmi

145 h syntaxin 1 in the absence of Munc18a, when syntaxin 1 is retained in the ER.

146 tory interaction between Munc18-1 and closed syntaxin 1 is well described, the mechanism of how Munc1

147 Syntaxin-1 is a key component of the synaptic vesicle do

148 Syntaxin-1 is a key component of the synaptic vesicle do

149 s suggest that binding of Munc18-1 to closed syntaxin-1 is a specialization that evolved to meet the

150 Because the main role of syntaxin-1 is as a target-SNARE for vesicle fusion, appe

151 more potent than the A-isoform, but not when syntaxin-1 is cleaved by botulinum neurotoxin C.

152 Importantly, the binding mode of CAPS1 to syntaxin-1 is distinct from that of Munc13-1; CAPS1 bind

153 the SNARE protein syntaxin-1, but only when syntaxin-1 is in a closed conformation that is incompati

154 yx-of-Held synapse from mutant mice in which syntaxin-1 is rendered constitutively open and SNARE-com

155 Syntaxin-1 is the central SNARE protein for neuronal exo

156 ntial for exocytosis, the function of closed syntaxin-1 is unknown.

157 es the ability to bind syntaxin-1 and rescue syntaxin-1 levels.

158 d two conserved residues (R151, I155) in the syntaxin-1 linker region as key sites for the MUN domain

159 ation tightly bound to Munc18-1, whereas the syntaxin-1 linker region changes its conformation, simil

160 uggest that the conformational change of the syntaxin-1 linker region induced by Munc13-1 initiates t

161 dicate that diffuse cytoplasmic and punctate syntaxin-1-LIR are present in different subsets of taste

162 The punctate syntaxin-1-LIR is believed to be associated with Golgi b

163 is present in type III cells while punctate syntaxin-1-LIR is present in type II cells.

164 Diffuse, cytoplasmic syntaxin-1-LIR is present in type III cells while puncta

165 All of the synapses associated with syntaxin-1-LIR taste cells are from type III cells onto

166 Cell death was too rapid after syntaxin-1 loss to study Golgi abnormalities.

167 yrosine (Y337A), which interacts with closed syntaxin-1, mildly increased secretory amplitude.

168 ction is important for a tripartite Munc18-1/syntaxin-1/MUN complex, in which syntaxin-1 still adopts

169 th occurs in cultured neurons upon depleting syntaxin-1, Munc18-1, and/or SNAP-25, well before synaps

170 As proteins, such as syntaxin-1, Munc18-1, or SNAP-25, modulate alpha-synucle

171 proteins involved in synaptic transmission (syntaxin-1, Munc18-1, SNAP-25), whereas other proteins i

172 n-neuronal Munc18 isoform that does not bind syntaxin-1, Munc18-3, in Munc18-1 KO neurons prevented c

173 Rescue experiments with syntaxin-1 mutants revealed that Munc18-1 recruitment to

174 t exhibits impaired activity with C-terminal syntaxin-1 mutants.

175 the same low-affinity binding of the extreme syntaxin-1 N terminus to Munc18-1, suggesting that this

176 ults reveal a striking interplay between the syntaxin-1 N-peptide and the conformational state of the

177 Previous in vitro studies suggested that the syntaxin-1 N-peptide is functionally important, whereas

178 hydrophobic pocket, which interacts with the syntaxin-1 N-terminal peptide, has been highly controver

179 SNARE complex through interactions with the syntaxin-1 N-terminal region that are critical for neuro

180 lethargy of unc-64 (C. elegans orthologue of syntaxin-1)-null mutants.

181 presynaptic, GB(1a)-containing receptors on syntaxin-1 opening and calcium entry to enhance probabil

182 , which activates SNARE complexes containing syntaxin-1 or -3, but not complexes containing syntaxin-

183 The loss of presynaptic proteins Munc18-1, syntaxin-1, or SNAP-25 is known to produce cell death, b

184 a demonstrate that cell death upon Munc18-1, syntaxin-1, or SNAP-25 loss occurs via a degenerative pa

185 Munc13s open Syntaxin-1, orchestrating SNARE complex assembly in an N

186 that the N-peptide and the H(abc)-domain of syntaxin-1 perform distinct and independent roles in syn

187 pecifically and reversibly connects multiple syntaxin 1/PI(4,5)P2complexes into larger mesoscale doma

188 ic vesicle priming and were proposed to open syntaxin-1, promoting SNARE complex assembly.

189 gans genetics, we show that the N-peptide of syntaxin-1 recruits the SM protein Munc18-1/nSec1 to the

190 cular events that control the degradation of syntaxin 1 remain undefined.

191 Modeling based on the known structure of syntaxin 1 revealed that these residues are exposed on t

192 e neuronal proteins synaptobrevin 1 (VAMP1), syntaxin 1, SNAP-25, and soluble N-ethylmaleimide-sensit

193 exocytosis of MSGs in neuroendocrine cells, syntaxin 1, SNAP-25, and VAMP2, were not involved in hom

194 nsmitter release includes the SNARE proteins syntaxin-1, SNAP-25 and synaptobrevin, which form a tigh

195 nesis, within 1-4 DIV upon loss of t-SNAREs (syntaxin-1, SNAP-25) or Munc18-1, but not v-SNAREs (syna

196 euron, SNARE/SM protein complexes containing syntaxin-1, SNAP-25, and Munc18-1 are preassembled in mi

197 ent protein (SNAP) receptor (SNARE) proteins syntaxin-1, SNAP-25, and synaptobrevin/VAMP (vesicle-ass

198 cts, double-labeling experiments showed that syntaxin-1, SNAP-25, synaptobrevin, and synaptophysin co

199 SNARE- and SM-protein complexes composed of syntaxin-1, SNAP-25, synaptobrevin-2/VAMP2, and Munc18-1

200 es containing preassembled t-SNARE proteins (syntaxin 1.SNAP-25), we determined how Munc18-1 controls

201 t to BoNT/C and E in neurons, can substitute syntaxin 1/SNAP-25 and prevent toxin-induced neuron deat

202 h neuronal cytotoxicity for BoNTs and reveal syntaxin 1/SNAP-25 as the ubiquitous and essential SNARE

203 ma membrane recycling processes that utilize syntaxin 1/SNAP-25, independent of synaptic vesicle exoc

204 so uncover interactions of membrane-anchored syntaxin-1/SNAP-25 heterodimers with the MUN domain, Mun

205 3/Munc13s may provide a template to assemble syntaxin-1/SNAP-25 heterodimers, leading to an acceptor

206 usion assay using VAMP2-containing donor and syntaxin-1/SNAP-25-containing acceptor liposomes.

207 te Munc18-1/syntaxin-1/MUN complex, in which syntaxin-1 still adopts a closed conformation tightly bo

208 Syntaxin-1 (Stx1) is a component of the synaptic vesicle

209 receptor (SNARE) complexes by SNARE proteins syntaxin-1 (Stx1), synaptosomal-associated protein 25 (S

210 chanisms: First, neuronal silencing promotes syntaxin-1 switch from a closed to an open conformation

211 e and requires that the target-SNARE protein syntaxin-1 switches from a closed to an open conformatio

212 lease depends on the SNARE complex formed by syntaxin-1, synaptobrevin and SNAP-25, as well as on com

213 The SNAREs Syntaxin-1, Synaptobrevin, and SNAP-25 play a central ro

214 ated proteins, such as VAMP (synaptobrevin), syntaxin-1, synaptophysin, synapsin Ia/b and IIa, munc-1

215 nock-down of syntabulin or disruption of the syntaxin-1-syntabulin-KIF5B complex impairs the anterogr

216 We now report that the complex of syntaxin-1-syntabulin-KIF5B mediates axonal transport of

217 C2D-F domains interact with the syntaxin-1 t-SNARE motif with maximum binding within the

218 veral other phenotypes as causal (defects in syntaxin-1 targeting and synaptic transmission).

219 The mutants rescued vesicle docking and syntaxin-1 targeting to the plasma membrane, with the ex

220 morphology, but not synaptic transmission or syntaxin-1 targeting.

221 ception of P335A that only supported partial syntaxin-1 targeting.

222 Munc18 binds to the closed conformation" of syntaxin 1, the ER-Golgi SM protein Sly1 interacts only

223 f the six different SNARE proteins examined [syntaxins 1 through 4 of 25-kDa synaptosome-associated p

224 proteins mediating synaptic vesicle fusion, syntaxin-1 uniquely includes an N-terminal peptide ('N-p

225 nformational states ("closed" vs. "open") of syntaxin-1 using PC12 cells and Caenorhabditis elegans.

226 The interaction of SNAP-29 with syntaxin-1 was further confirmed with immunoprecipitatio

227 Binding of Munc18-1 to syntaxin-1 was impaired in syntaxin-1B(Open) synapses, a

228 ensitive factor attachment protein receptor) syntaxin-1 was shown previously to be present on putativ

229 rmation, similar to that of the LE mutant of syntaxin-1 when bound to Munc18-1.

230 ritical role in intracellular trafficking of syntaxin-1, which is dependent on the conformational sta

231 al a novel mode of binding between CAPS1 and syntaxin-1, which play a crucial role in neurosecretion.

232 APS1 binds to the full-length of cytoplasmic syntaxin-1 with preference to its "open" conformation, w

233 Expression of Munc18-1, which recruits syntaxin-1 within the exocytotic pathway, does not modul