ライフサイエンスコーパス: GAT1

1 GAT1 also behaved as an SKF89976A-sensitive water channe

2 GAT1 function also is regulated by transporter substrate

3 GAT1 of Candida albicans encodes a GATA-factor homologou

4 GAT1 stoichiometry was determined by measuring GABA-evok

5 GAT1 was expressed in Xenopus oocytes and studied electr

6 rtridge carry 9000, 7.8 million, and 430,000 GAT1 molecules, respectively; 61-63% of these molecules

7 GABA transporter subtype 1 (GAT1) knock-out (KO) mice display normal reproduction an

8 GABA transporter subtype 1 (GAT1) molecules were counted near GABAergic synapses, to

9 eactive for the GABA membrane transporter 1 (GAT1) or the calcium-binding protein parvalbumin (PV) an

10 amma-Aminobutyric acid (GABA) transporter 1 (GAT1)(1) regulates neuronal excitation of the central ne

11 eting gamma-aminobutyric acid transporter 1 (GAT1), the most abundant gamma-aminobutyric acid (GABA)

12 plasma membrane such as GABA transporter 1 (GAT1), were not present.

13 y low gamma-aminobutyric acid transporter-1 (GAT1)-like immunoreactivity.

14 pocampus have a membrane density of 800-1300 GAT1 molecules per square micrometer, and the axons that

15 is depolarization and calcium dependent; (3) GAT1 internalization is associated with clathrin and dyn

16 connect boutons have a linear density of 640 GAT1 molecules per micrometer.

17 induced surface expression is unchanged in a GAT1 mutant lacking tyrosine phosphorylation sites.

18 polymerization, in contrast, does not affect GAT1 membrane mobility.

19 nt study was to discover novel high affinity GAT1 binders by screening of biphenyl focused pseudostat

20 encode a class I glutamine amidotransferase (GAT1), a superfamily for which Arabidopsis (Arabidopsis

21 ence of interactions between syntaxin 1A and GAT1 comes from three experimental approaches: botulinum

22 acitance, transport-associated currents, and GAT1-specific charge movements.

23 ), relatively selective blockers of GAT3 and GAT1 isoforms, respectively.

24 The specific SGLT1 and GAT1 Lp values were obtained by measuring Lp in the pres

25 he Lp values of oocytes expressing SGLT1 and GAT1 were indistinguishable from the Lp of control oocyt

26 5)) for Cl(-) of 21 and 115 mm for SGLT1 and GAT1, respectively.

27 vesicle release and recycling, reduce basal GAT1 expression and prevent PKC-induced translocation.

28 Fusions between GAT1 and green fluorescent protein (GFP) were tested in

29 ffects by regulating the interaction between GAT1 and syntaxin 1A.

30 ampal neurons that endogenously express both GAT1 and syntaxin 1A, substrate application results in a

31 Thus, in both GAT1 and SGLT1, Cl(-) modulates the kinetics of cotransp

32 that is gated by GABA and Na+ and blocked by GAT1 antagonists.

33 However, Cl(-) was transported by GAT1 because the inward movement of 2 positive charges w

34 tic cleft by inhibiting its reuptake carrier GAT1 is an established approach for the treatment of CNS

35 es approximately one-third of total cellular GAT1.

36 Upon cloning, GAT1 transcription was, as predicted, NCR-sensitive and

37 We determined the interactions that confine GAT1 at the membrane by investigating the lateral mobili

38 Our data reveal that actin confines GAT1 to the plasma membrane via ezrin, and this interact

39 oimmunoprecipitation of a complex containing GAT1 and syntaxin 1A.

40 cid (GABA) and Na(+)/glucose cotransporters (GAT1 and SGLT1, respectively) expressed in Xenopus laevi

41 Calcium depletion decreases GAT1 surface expression by diminishing the recycling poo

42 tamate, and serotonin receptors downregulate GAT1 function.

43 As expected, we found that blocking either GAT1 or GAT3 prolonged oscillations.

44 These data demonstrate (1) that endogenous GAT1 function can be regulated by PKC via subcellular re

45 c strategy that targets the widely expressed GAT1 transporter system.

46 s, (ii) does not occur in oocytes expressing GAT1 alone, and (iii) does not occur in oocytes expressi

47 In oocytes expressing GAT1 and syntaxin 1A, superfusion of transporter substra

48 he transporter (IL4) into oocytes expressing GAT1 greatly reduced both forward and reverse transport

49 ysiologically as well as with [3H]GABA flux; GAT1 was also expressed in mammalian cells and studied w

50 formance of our approach is demonstrated for GAT1, the most important GABA transporter (GAT) subtype.

51 -glucose (SGLT1) and the human Na+-Cl--GABA (GAT1) cotransporters were expressed in Xenopus laevis oo

52 catabolite repression (NCR)-sensitive (GAP1, GAT1, DAL5) and retrograde (CIT2, DLD3, IDH1/2) gene exp

53 ong five effectors (TAP42, MKS1, URE2, GLN3, GAT1) of the Tor proteins, and identify how the quality

54 r vesicles to the plasma membrane; at higher GAT1 expression levels, activators of PKC fail to induce

55 similar observations were obtained for human GAT1 and mouse GAT4.

56 py structure of full-length, wild-type human GAT1 in complex with its clinically used inhibitor tiaga

57 Two observations implicated GAT1 in nitrogen regulation.

58 flux and efflux was mimicked by mutations in GAT1 at the syntaxin 1A binding site.

59 transmission in the mGAT1 KO mice, including GAT1-independent GABA uptake, number of GABAergic intern

60 Sucrose increases GAT1 surface expression by blocking clathrin- and dynami

61 ession, i.e., as DAL80 expression increases, GAT1 expression decreases.

62 otein receptor (SNARE) protein that inhibits GAT1 transport rates via interactions with the N-termina

63 clathrin and dynamin; and (4) intracellular GAT1 is associated with multiple compartments and, more

64 Intraseptal GAT1-SAP treatment did not alter baseline or behaviorall

65 rmance in DNMTP were impaired by intraseptal GAT1-SAP.

66 The growth of mutants lacking GAT1 was reduced when isoleucine, tyrosine or tryptophan

67 n ( approximately 50%) of membrane-localized GAT1 is immobile on the time scale investigated ( approx

68 Our structure reveals that tiagabine locks GAT1 in the inward-open conformation, by blocking the in

69 At low GAT1 expression levels, activators of protein kinase C (

70 We also identified ezrin as a major GAT1 adaptor to actin.

71 Moreover, GAT1-SAP did not alter evoked hippocampal ACh efflux rel

72 Mouse GAT1 (mGAT1) KO mice exhibit motor disorders, including

73 Mutant GAT1 proteins, in which most or all of a leucine heptad

74 A mutant GAT1 construct that was refractory to tyrosine phosphory

75 nscription factors GLN3 and NIL1 (also named GAT1).

76 sion with GABA-free solutions or addition of GAT1 inhibitors SKF89976-A or SKF100330-A.

77 onic acid decreased the apparent affinity of GAT1 and SGLT1 for Na(+) and the organic substrate.

78 ith transporter ligands alters the amount of GAT1 tyrosine phosphorylation, and substrate-induced sur

79 change (i) is prevented by coapplication of GAT1 antagonists, (ii) does not occur in oocytes express

80 ibility that the subcellular distribution of GAT1 is associated with mutually exclusive transporter p

81 layers, whereas the laminar distribution of GAT1-positive cartridges did not change.

82 The N-terminal cytoplasmic domain of GAT1 directly interacts with syntaxin 1A; this interacti

83 diated through the PDZ-interacting domain of GAT1.

84 Based upon estimates of GAT1 molecules in cortical boutons, the present data sug

85 Specifically, the perisynaptic expression of GAT1 enables it to regulate GABA levels near synapses an

86 Ectopic expression of GAT1 in mature leaves increased plasmodesmal permeabilit

87 Expression of GAT1 is shown to be NCR sensitive, partially Gln3p depen

88 In support of this hypothesis, incubation of GAT1-expressing cells with transporter ligands alters th

89 e insights into the mixed-type inhibition of GAT1 by tiagabine, which is an important anticonvulsant

90 can be influenced by the relative levels of GAT1 and URE2 expression.

91 ensity in an electron cryo-microscopy map of GAT1.

92 ane by investigating the lateral mobility of GAT1-yellow fluorescent protein-8 (YFP8) expressed in ne

93 r tiagabine into a protein homology model of GAT1 allowed derivation of a common binding mode for thi

94 th a decrease in tyrosine phosphorylation of GAT1 and resulted in a redistribution of the transporter

95 ich substrates permit the phosphorylation of GAT1 on tyrosine residues and that the phosphorylated st

96 t promote direct tyrosine phosphorylation of GAT1 promote a relative increase in surface GAT1 levels,

97 t determination of the inhibitory potency of GAT1 inhibitors, is capable of identifying those inhibit

98 ization rates also occurs in the presence of GAT1 substrates, suggesting the hypothesis that tyrosine

99 tein kinase C (PKC) induce redistribution of GAT1 from intracellular vesicles to the plasma membrane;

100 which are known to cause a redistribution of GAT1 from the cell surface, were additive to the effects

101 hibition correlates with a redistribution of GAT1 from the plasma membrane to intracellular locations

102 modulation by PKC, delineating one region of GAT1 necessary for its targeting.

103 Thus, functional regulation of GAT1 in oocytes occurs via components common to transpor

104 ntial trigger for the cellular regulation of GAT1 signaling by tyrosine phosphorylation.

105 d for the substrate-induced up-regulation of GAT1 surface expression.

106 on is due, at least in part, to a slowing of GAT1 internalization in the presence of extracellular GA

107 The presented structure of GAT1 gives crucial insights into the biology and pharmac

108 ACHC and nipecotic acid, both substrates of GAT1, up-regulate transport; GAT1 transport inhibitors t

109 onding to the N-terminal cytoplasmic tail of GAT1 reversed the IL4-mediated inhibition; this reversal

110 via interactions with the N-terminal tail of GAT1 was unable to regulate the GAT1 IL4 mutant.

111 rtic acid residues in the N-terminal tail of GAT1.

112 f Gln3p and Dal80p binding sites upstream of GAT1.

113 rug potentially exerting a similar effect on GAT1.

114 ously that syntaxin 1A exerts its effects on GAT1 by decreasing the net uptake of GABA and its associ

115 erts its effects, directly or indirectly, on GAT1 function through interactions with GAT1's N-termina

116 ormed variant interpretation and research on GAT1 function.

117 eport, we show that two tyrosine residues on GAT1 contribute to the phosphorylation and transporter r

118 In oocytes, GAT1 generates no outward current in a similar voltage r

119 expressing syntaxin 1A and wild-type GAT1 or GAT1 mutants.

120 drive the selective inhibition of GAT3 over GAT1.

121 essengers, and interacting proteins regulate GAT1 trafficking.

122 affect tyrosine kinase activity to regulate GAT1 serine phosphorylation requires a change in its tyr

123 ates receptor tyrosine kinases, up-regulated GAT1 function suggesting one potential trigger for the c

124 ggest that substrate translocation regulates GAT1-syntaxin 1A interactions and provide a mechanism by

125 rgic lesions of the MSDB using GAT1-saporin (GAT1-SAP) and examined on spontaneous exploration (Exper

126 The binding site GAT1 mutant also caused a reduction in exchange.

127 The model then accounts for some GAT1 kinetic data as well.

128 In the absence of substrate, GAT1 and SGLT1 exhibited charge movements that manifeste

129 Protein kinase C decreases surface GAT1 expression by increasing the endocytosis rate, but

130 GAT1 promote a relative increase in surface GAT1 levels, and this results from a slowing of the tran

131 ivity promote a relative decrease in surface GAT1 levels; whether this effect is caused by direct tra

132 These data support the ideas that GAT1 can exist in either of two mutually exclusive phosp

133 The implication of this result is that GAT1 can mediate electrogenic (electrophoretic) influx o

134 1,10 or copper-regulated CUP1 promoter, that GAT1 expression is inversely regulated by the level of D

135 The present experiments show that GAT1 is phosphorylated on serine residues in a PKC-depen

136 Recent evidence shows that GAT1 substrates, second messengers, and interacting prot

137 ster resonance energy transfer suggests that GAT1-YFP8 and cyan fluorescent (CFP) tagged ezrin (ezrin

138 The GAT1 transmembrane domains 1, 6 and extracellular loop 4

139 0 value of 168 microM, and is blocked by the GAT1 inhibitor SKF89976A.

140 Experimental testing further confirmed the GAT1 inhibiting properties of this thyroid hormone.

141 a Cl(-)/Cl(-) exchange mechanism during the GAT1 transport cycle.

142 We propose a role for the GAT1 thioredoxin in the redox regulation of callose depo

143 s an alternative, a channel may exist in the GAT1 protein that is gated by GABA and Na+ and blocked b

144 was associated with loss-of-function in the GAT1 transporter activity.

145 sion of transporter substrates increases the GAT1 transport rate.

146 depolymerizing actin or by interrupting the GAT1 postsynaptic density 95/Discs large/zona occludens

147 al data guided docking of derivatives of the GAT1 inhibitor tiagabine into a protein homology model o

148 and transport proteins, the promoters of the GAT1, DAL80, and DEH1 genes all contain multiple GATA se

149 ial associations of variant positions on the GAT1 3D structure with variant pathogenicity, altered mo

150 inal tail of GAT1 was unable to regulate the GAT1 IL4 mutant.

151 Thus, the GAT1 stoichiometry was 2Na(+):1GABA.

152 L-proline transporter (PROT) belongs to the GAT1 gene family, which includes Na- and Cl-dependent pl

153 her, these data suggest a model in which the GAT1 IL4 domain serves as a barrier for transport, and t

154 phrine, epinephrine) transporters within the GAT1/NET gene family and possesses conserved residues im

155 This GAT1-mediated outward current occurs only after applying

156 In the present study we examine three GAT1 modulators.

157 ch then leads to electrogenic efflux through GAT1 at positive voltages.

158 Increased extracellular GABA, through GAT1 blockade, enhances the affinity of GABAA receptors

159 id not observe passive Na+ transport through GAT1.

160 the fraction of syntaxin 1A that is bound to GAT1 on a time-scale comparable to the substrate-induced

161 h substrates of GAT1, up-regulate transport; GAT1 transport inhibitors that are not transporter subst

162 that the gamma-aminobutyric acid transporter GAT1 is regulated by direct tyrosine phosphorylation, re

163 at brain gamma-aminobutyric acid transporter GAT1, and other members of the neurotransmitter transpor

164 The rat brain GABA transporter GAT1 and other members of this family are regulated by d

165 synaptic transmitter by the GABA transporter GAT1 depends on the previous binding of Na+ and Cl-, and

166 by examining the rat brain GABA transporter GAT1 endogenously expressed in hippocampal neurons.

167 l cytoplasmic domain of the GABA transporter GAT1 regulated substrate transport rates.

168 that the trafficking of the GABA transporter GAT1 resembles the trafficking of neurotransmitter-fille

169 essing the cloned rat brain GABA transporter GAT1.

170 essing the cloned rat brain GABA transporter GAT1.

171 nd charge movements for the GABA transporter GAT1.

172 ates during function of the GABA transporter GAT1.

173 n gamma-aminobutyric acid (GABA) transporter GAT1 expressed endogenously in hippocampal neurons and e

174 n gamma-aminobutyric acid (GABA) transporter GAT1.

175 r domains of the rat brain GABA transporter (GAT1) contribute to the transport process.

176 , osteopontin (SPP1) and a GABA transporter (GAT1)-we discover undocumented phosphorylation, glycosyl

177 f body weight), a GABA membrane transporter (GAT1) blocker, in 17 off-medication patients with schizo

178 ed with the cDNA for a rat GABA transporter, GAT1, cloned downstream of a T7 RNA polymerase promoter.

179 genous gamma-aminobutyric acid transporters (GAT1) in cortical neurons that comprises approximately o

180 both wild-type and mutant GABA transporters (GAT1) expressed in Xenopus oocytes using a combination o

181 The GABA transporters (GAT1, GAT2, GAT3, and BGT1) have mostly been discussed i

182 gulated by two astrocytic GABA transporters, GAT1 and GAT3, which are localized near and far from syn

183 In turn, GAT1 expression is Gln3p dependent and Dal80p regulated

184 systems expressing syntaxin 1A and wild-type GAT1 or GAT1 mutants.

185 re given GABAergic lesions of the MSDB using GAT1-saporin (GAT1-SAP) and examined on spontaneous expl

186 manner, but this state is only revealed when GAT1 tyrosine phosphorylation is eliminated or greatly r

187 , on GAT1 function through interactions with GAT1's N-terminal tail and that the inhibition occurs at

188 er, coinjection of total rat brain mRNA with GAT1 permits PKC-mediated modulation at high transporter

189 ses this mGAT1-GFP fusion in place of the WT GAT1 gene.

190 rafficking similar to that of wild-type (WT) GAT1.