ライフサイエンスコーパス: dysbindin

1 g proteins, Pallidin, Muted, Cappuccino, and Dysbindin.

2 ne encoding the dystrobrevin-binding protein dysbindin.

3 ic mutations in a schizophrenia risk factor, dysbindin.

4 dentified RhoA as a novel binding partner of Dysbindin.

5 in myoblasts resulted in elevated levels of dysbindin.

6 tions in the gene encoding the novel protein dysbindin-1 (DTNBP1) are among the most commonly reporte

7 The gene for dysbindin-1 (DTNBP1) is located at 6p and has also been

8 an hippocampal formations revealed that both dysbindin-1 and snapin are concentrated in tissue enrich

9 trophysiological deficits related to reduced dysbindin-1 and the potential role of PV cells, we exami

10 Further studies of dysbindin-1 and the proteins with which it interacts can

11 ucleotide polymorphisms in the gene encoding dysbindin-1 at 6p22.3.

12 Dysbindin-1 disruption altered dopamine-related behavior

13 The gene encoding dysbindin-1 has recently been implicated in susceptibili

14 ric diagnoses, suggesting a general role for dysbindin-1 in cognition.

15 In contrast to the role of dysbindin-1 in glutamatergic transmission, gamma-band ab

16 We found that reduced dysbindin-1 in mice yielded deficits in auditory-evoked

17 The function of dysbindin-1 in presynaptic, postsynaptic and microtubule

18 ate here that snapin is a binding partner of dysbindin-1 in vitro and in the brain.

19 Dysbindin-1 is best known as dystrobrevin-binding protei

20 nding, immunoelectron microscopy showed that dysbindin-1 is located in (i) synaptic vesicles of axosp

21 et al. show that, contrary to expectations, dysbindin-1 is located presynaptically in glutamatergic

22 ound between case-control differences in any dysbindin-1 isoform and the case-control differences in

23 ver, if the protein reductions encompass all dysbindin-1 isoforms or if they are associated with decr

24 How dysbindin-1 might affect glutamate release nevertheless

25 axon terminal loss or neuroleptic effects on dysbindin-1 or VGluT-1.

26 izophrenia populations displayed presynaptic dysbindin-1 reductions averaging 18-42% (P = 0.027-0.000

27 bindin-1C and known post-synaptic effects of dysbindin-1 reductions in the rodent equivalent of the D

28 Our findings indicate that presynaptic dysbindin-1 reductions independent of the dystrophin gly

29 Dysbindin-1 regulates D2-receptor trafficking and is imp

30 The dominant circuit impact of reduced dysbindin-1 was impaired inhibition, and PV cell immunor

31 oded protein dystrobrevin-binding protein 1 (dysbindin-1) is often reduced in excitatory cortical lim

32 ctional roles of the three major isoforms of dysbindin-1, (A, B, and C) remain unknown, we generated

33 Dysbindin-1, a protein that regulates aspects of early a

34 ne-protein phosphatase-alpha (RPTPalpha) and dysbindin-1, each of which reduces Src activity via prot

35 ion of this gene and of its encoded protein, dysbindin-1, have been reported in the brains of schizop

36 We explored in dysbindin-1-deficient mice (dys-/-) (1) schizophrenia-re

37 t mouse, dys-1A(-/-), with selective loss of dysbindin-1A and investigated schizophrenia-related phen

38 icant reductions in dysbindin-1C (but not in dysbindin-1A or -1B) in schizophrenia (P = 0.022).

39 Loss of dysbindin-1A resulted in heightened initial exploration

40 idence for differential functional roles for dysbindin-1A vs dysbindin-1C isoforms among phenotypes r

41 Loss of dysbindin-1A was not associated with disruption of eithe

42 ing DISC1 (disrupted in schizophrenia 1) and dysbindin-1B are found in insoluble forms within brain h

43 x (DLPFC) revealed significant reductions in dysbindin-1C (but not in dysbindin-1A or -1B) in schizop

44 predominantly post-synaptic localization of dysbindin-1C and known post-synaptic effects of dysbindi

45 mRNA translation and/or processes promoting dysbindin-1C degradation (e.g. oxidative stress, phospho

46 the present findings suggest that decreased dysbindin-1C in the DLPFC may contribute to the cognitiv

47 rential functional roles for dysbindin-1A vs dysbindin-1C isoforms among phenotypes relevant to the p

48 Consequently, the mean 60% decrease in dysbindin-1C observed in 71% of our case-control pairs a

49 ed a concomitant change in the expression of dysbindin-1C.

50 structural homologue of the acidic domain of dysbindin, a component of the dystrophin-associated prot

51 teins and identified a critical function for dysbindin, a gene linked to schizophrenia in humans.

52 is screen identified a critical function for dysbindin, a gene linked to schizophrenia in humans.

53 we found that TRIM32 binds and ubiquitinates dysbindin, a protein implicated in the genetic aetiology

54 itive to genetic defects in a locus encoding dysbindin, a protein required for synapse biology and im

55 Last, levels of dysbindin, a regulator of the membrane availability of d

56 Here, we show that dysbindin, a schizophrenia-susceptibility gene widely ex

57 genes encoding the schizophrenia risk factor dysbindin, a subunit of the biogenesis of lysosome-relat

58 a susceptibility gene DTNBP1 and its product dysbindin, a subunit of the BLOC-1 complex, and describe

59 t of late endosomes (LEs) and interacts with dysbindin, a subunit of the endosomal sorting complex BL

60 schizophrenia, but little is known about how dysbindin affects neuronal function in the circuitry und

61 promote dysbindin decay but rather protected dysbindin against degradation by TRIM32.

62 We found 491 proteins sensitive to dysbindin and BLOC-1 loss of function.

63 otrusions, and reveal the essential roles of dysbindin and CaMKIIalpha in the stabilization of dendri

64 Our data identify TRIM32 as a regulator of dysbindin and demonstrate that the LGMD2H/STM mutations

65 echanism of post-translational regulation of dysbindin and hypertrophy via TRIM24 and TRIM32 and show

66 hermore, the D487N mutant could bind to both dysbindin and its E2 enzyme but was defective in monoubi

67 of function mutations in the genes encoding dysbindin and its interacting BLOC-1 subunits.

68 echanisms controlling the cellular levels of dysbindin and its interacting partners may participate i

69 These data suggest that the acidic domain of dysbindin and its paralogs in humans may function to rec

70 94H impair ubiquitin ligase activity towards dysbindin and were mislocalized in heterologous cells.

71 g to a deletion in the gene Dtnbp1 (encoding dysbindin) and that mutation of the human ortholog DTNBP

72 enia, including the DISC1, COMT, neuregulin, dysbindin, and alpha-7 nicotinic receptor genes, appear

73 Furthermore, we demonstrated that Arp2/3, dysbindin, and subunits of the BLOC-1 complex biochemica

74 e DTNBP1 (dystrobrevin-binding protein 1, or dysbindin) are strongly associated with schizophrenia.

75 ow performed a yeast two-hybrid screen using dysbindin as bait against a cardiac cDNA library to iden

76 Dysbindin assembles into the biogenesis of lysosome-rela

77 Dysbindin/BLOC-1 and ATP7A genetically and biochemically

78 Human dysbindin/BLOC-1 coprecipitates with NSF and vice versa,

79 fusion machinery as factors downregulated in dysbindin/BLOC-1 deficiency in neuroectodermal cells and

80 Our results demonstrate that dysbindin/BLOC-1 expression defects result in altered ce

81 tides whose cellular content is sensitive to dysbindin/BLOC-1 loss of function.

82 Dysbindin/BLOC-1 loss-of-function alleles do not affect

83 To test the hypothesis that NSF and dysbindin/BLOC-1 participate in a pathway-regulating syn

84 ein networks, or interactomes, downstream of dysbindin/BLOC-1 remain partially explored despite their

85 ic function, we examined the role for NSF in dysbindin/BLOC-1-dependent synaptic homeostatic plastici

86 and dependent factors in the hippocampus of dysbindin/BLOC-1-null mice.

87 ouse null alleles muted (Bloc1s5(mu/mu)) and dysbindin (Bloc1s8(sdy/sdy)).

88 n of the schizophrenia susceptibility factor dysbindin (Bloc1s8) or two other dysbindin-interacting p

89 In addition, mutation of human Dysbindin causes HPS type 7.

90 BP1, or other factors that also downregulate dysbindin, compromise the ability of BLOC-1 to traffic D

91 Thus, dysbindin controls hippocampal LTP by selective regulati

92 urprisingly, however, TRIM24 did not promote dysbindin decay but rather protected dysbindin against d

93 polymerization complex Arp2/3 is reduced in dysbindin-deficient cells, thus affecting actin-dependen

94 However, mechanisms engaged by dysbindin defining schizophrenia susceptibility pathways

95 Although intact dysbindin did not bind any CK1 isoform, deletion of its

96 In contrast, decreased dysbindin did not change dopamine D1 receptor (DRD1) lev

97 B (cAMP response element-binding protein) in dysbindin downregulated cells, demonstrating enhanced in

98 The schizophrenia-susceptibility gene dysbindin (DTNBP1 on 6p22.3) encodes a neuronal protein

99 ptibility loci relates to the genes encoding dysbindin (DTNBP1) and neuregulin (NRG1).

100 the evidence to be strong are those encoding dysbindin (DTNBP1) and neuregulin 1 (NRG1).

101 nctionally interacts with the fly homolog of Dysbindin (DTNBP1) via direct protein-protein interactio

102 rder in multiple previous studies, including dysbindin (DTNBP1), neuregulin (NRG1), and disrupted-in-

103 es--catechol-O-methyl transferase (COMT) and dysbindin (dys; dystrobrevin-binding protein 1 (DTNBP1))

104 ons in the schizophrenia susceptibility gene dysbindin (dysb), in isolation or in combination with nu

105 Little is known about dysbindin expression in normal or schizophrenic brain.

106 Dysbindin expression is reduced in schizophrenic brain t

107 rated an association between variants in the dysbindin gene (DTNBP1) and schizophrenia.

108 o determine whether genetic variation in the dysbindin gene affects cortical dysbindin mRNA levels.

109 Disruption of the dysbindin gene dramatically increased NR2A-mediated syna

110 Although no mutations in the dysbindin gene have been found, the recent identificatio

111 d neurons in mice carrying a deletion in the dysbindin gene have fewer dendritic spines.

112 ficient to rule out the possibility that the dysbindin gene is not the actual susceptibility gene, bu

113 Findings suggest that the human dysbindin gene may play a role in the susceptibility to

114 Disruption of dysbindin gene resulted in a marked decrease in the exci

115 In each subject, 10 polymorphisms in the dysbindin gene were genotyped and assessed.

116 ied statistically significantly according to dysbindin genotype.

117 eduction of NSF alone or in combination with dysbindin haploinsufficiency impaired homeostatic synapt

118 g the HPS phenotype in humans, indicate that dysbindin has a role in the biogenesis of lysosome-relat

119 Dysbindin has been implicated in the pathogenesis of sch

120 o studies should examine the significance of Dysbindin in cardiomyopathy.

121 ant Sandy mice, we have explored the role of dysbindin in dopamine signaling and neuronal function in

122 istently, we found that TRIM32 also degraded dysbindin in neonatal rat ventricular cardiomyocytes as

123 ported earlier as an E3 ubiquitin ligase for dysbindin in skeletal muscle.

124 conclusion, we show a novel cardiac role of Dysbindin in the activation of RhoA-SRF and MEK1-ERK1 si

125 s has revealed reduced levels of the protein dysbindin in the brains of those suffering from the neur

126 These findings elucidate the function of dysbindin in the dynamic morphogenesis of dendritic prot

127 d mechanistic characterization revealed that Dysbindin induced cardiac hypertrophy via RhoA-SRF and M

128 lity factor dysbindin (Bloc1s8) or two other dysbindin-interacting polypeptides, which assemble into

129 NA and protein levels of key components of a dysbindin interaction network by, quantitative real time

130 ed Ca(2+) sensor, we demonstrate that snapin-dysbindin interaction regulates SV positional priming th

131 he expression of components belonging to the dysbindin interactome and these molecular differences ma

132 cardiac cDNA library to identify the cardiac dysbindin interactome.

133 1 encodes a polypeptide that assembles, with dysbindin, into the octameric BLOC-1 complex.

134 We also show that dysbindin is a component of the biogenesis of lysosome-r

135 ndent samples provides further evidence that dysbindin is a possible schizophrenia susceptibility gen

136 We have previously shown that dysbindin is a potent inducer of cardiomyocyte hypertrop

137 Dysbindin is a schizophrenia susceptibility factor and s

138 Dysbindin is a schizophrenia susceptibility gene require

139 Dysbindin is a ubiquitously expressed protein that binds

140 Dysbindin is an established schizophrenia susceptibility

141 These data add to the evidence that dysbindin is an etiologic factor in schizophrenia risk.

142 Thus, dysbindin is essential for adaptive neural plasticity an

143 Because Dysbindin is highly expressed in the heart, we aimed her

144 We found that dysbindin is required presynaptically for the retrograde

145 Our results show that dysbindin is required to stabilize dendritic protrusions

146 We conclude that further investigation of dysbindin is warranted.

147 The DTNBP1 gene, encoding dysbindin, is now generally considered to be a susceptib

148 Using a dysbindin knockout line (dys(-/-)) derived from the natu

149 Hence, dysbindin might contribute to the spine pathology of sch

150 Dysbindin mRNA is expressed widely in the brain, and its

151 enia had statistically significantly reduced dysbindin mRNA levels in multiple layers of the dorsolat

152 ls in the dorsolateral prefrontal cortex and dysbindin mRNA levels in the midbrain by in situ hybridi

153 Variation in dysbindin mRNA levels may be determined in part by varia

154 Cortical dysbindin mRNA levels varied statistically significantly

155 Dysbindin mRNA levels were quantitatively reduced in the

156 ation in the dysbindin gene affects cortical dysbindin mRNA levels.

157 Dysbindin mRNA was detected in the frontal cortex, tempo

158 This dysbindin mutant phenotype is fully rescued by presynapt

159 out line (dys(-/-)) derived from the natural dysbindin mutant Sandy mice, we have explored the role o

160 ic risk factors for schizophrenia, including dysbindin, neuregulin 1, DAOA, COMT, and DISC1, and neur

161 PI4KIIalpha content in the dentate gyrus of dysbindin-null BLOC-1 deficiency and AP-3-null mice.

162 proteomics combined with genetic analyses in dysbindin-null mice (Mus musculus) and the genome of sch

163 ot NR2B, in hippocampal neurons derived from dysbindin-null mutant mice (Dys-/-).

164 he hyperactivity of dendritic protrusions in dysbindin-null neurons is attributed in part to decrease

165 In dysbindin-null neurons, dendritic protrusions are hypera

166 rescued by presynaptic expression of either dysbindin or Drosophila NSF.

167 fied a robust activation of SRF signaling by Dysbindin overexpression that was associated with signif

168 iously described, we found that mutations in dysbindin precluded homeostatic synaptic plasticity elic

169 ystems have shown that Snapin interacts with Dysbindin, prompting us to test whether Snapin might be

170 show that the sdy mutant mouse expresses no dysbindin protein owing to a deletion in the gene Dtnbp1

171 DTNBP1 siRNA decreased dysbindin protein, increased cell surface DRD2 and block

172 The expression of dysbindin proteins is decreased in the brains of schizop

173 eal subunit-specific regulation of NMDARs by dysbindin, providing an unexpected link between these tw

174 Exogenous expression of dysbindin reduced NR2A surface expression in both wild-t

175 Taken together, these results suggest that dysbindin regulates PFC function by facilitating D2-medi

176 It has yet to be determined whether dysbindin regulates the dynamics of dendritic protrusion

177 henotypes in two cellular compartments where dysbindin resides, endosomes and presynapses.

178 These results elucidate dysbindin's modulation of D2-related behavior, cortical

179 with schizophrenia and controls, we compared dysbindin, synaptophysin, spinophilin, and cyclophilin m

180 ggests that snapin functions in concert with dysbindin to modulate vesicle release and possibly homeo

181 tion of SRF signaling and hypertrophy due to dysbindin, whereas TRIM24 promoted these effects in neon

182 trobrevin-binding protein 1 (DTNBP1) encodes dysbindin, which along with its binding partner Muted is

183 The authors hypothesized that dysbindin, which is a probable susceptibility gene for s

184 ning the schizophrenia susceptibility factor dysbindin, which is encoded by the gene DTNBP1.

185 d molecular mechanisms of the association of dysbindin with psychosis.