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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

34 es approximately one-third of total cellular GAT1.

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

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

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

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

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

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

41 tamate, and serotonin receptors downregulate GAT1 function.

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

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

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

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

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

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

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

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

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

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

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

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

54 Two observations implicated GAT1 in nitrogen regulation.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

70 A mutant GAT1 construct that was refractory to tyrosine phosphory

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

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

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

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

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

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

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

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

79 diated through the PDZ-interacting domain of GAT1.

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

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

82 Ectopic expression of GAT1 in mature leaves increased plasmodesmal permeabilit

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

105 f Gln3p and Dal80p binding sites upstream of GAT1.

106 rug potentially exerting a similar effect on GAT1.

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

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

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

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

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

112 essengers, and interacting proteins regulate GAT1 trafficking.

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

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

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

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

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

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

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

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

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

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

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

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

125 1,10 or copper-regulated CUP1 promoter, that GAT1 expression is inversely regulated by the level of D

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

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

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

129 0 value of 168 microM, and is blocked by the GAT1 inhibitor SKF89976A.

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

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

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

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

134 sion of transporter substrates increases the GAT1 transport rate.

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

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

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

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

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

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

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

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

143 This GAT1-mediated outward current occurs only after applying

144 In the present study we examine three GAT1 modulators.

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

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

147 id not observe passive Na+ transport through GAT1.

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

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

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

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

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

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

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

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

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

157 essing the cloned rat brain GABA transporter GAT1.

158 essing the cloned rat brain GABA transporter GAT1.

159 nd charge movements for the GABA transporter GAT1.

160 ates during function of the GABA transporter GAT1.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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