ライフサイエンスコーパス: dystrobrevin

1 es lacking neuronal dystrobrevin (i.e., beta-dystrobrevin).

2 e other known dystrobrevin (now termed alpha-dystrobrevin).

3 P2 and the other composed of alpha- and beta-dystrobrevin.

4 plice forms of this gene which we have named dystrobrevin.

5 h its EF-hand 1 domain, interacts with alpha-dystrobrevin.

6 interacting with another cytosolic protein, dystrobrevin.

7 presence of alpha-dystrobrevin but not beta-dystrobrevin.

8 omponents of the DAP complex, syntrophin and dystrobrevin.

9 played normal localization of syntrophin and dystrobrevin.

10 nd its relationship to the distantly related dystrobrevins.

11 tinct properties of association on the alpha-dystrobrevins.

12 o key DGC signaling-related molecules: alpha-dystrobrevin 1 (global MIFs) and syntrophin beta1 (globa

13 minate in skeletal muscle: full-length alpha-dystrobrevin-1 (84 kD), and COOH-terminal truncated alph

14 Thus, the distinct distributions of alpha-dystrobrevin-1 and -2 can be partly explained by specifi

15 tion of the intracellular signaling proteins dystrobrevin-1 and -2, alpha- and beta1-syntrophin and n

16 ctive reduction in the localization of alpha-dystrobrevin-1 and -2, alpha- and beta1-syntrophin, and

17 restores the sarcolemmal expression of alpha-dystrobrevin-1 and -2, and beta1- and beta2-syntrophin i

18 ignalosome by the C-terminal domain of alpha-dystrobrevin-1 and not the closely related splice varian

19 strobrevin-2 binds dystrophin, whereas alpha-dystrobrevin-1 binds both dystrophin and utrophin.

20 alpha-Dystrobrevin-1 is associated with Dp71, utrophin, and sy

21 By contrast, alpha-dystrobrevin-1 is found in perivascular astrocytes and B

22 In contrast, alpha-dystrobrevin-1 is more highly restricted to the synapse,

23 In contrast, alpha-dystrobrevin-1 remained synaptically localized in mdx an

24 -1(lf) were partially rescued by mouse alpha-dystrobrevin-1.

25 1 (84 kD), and COOH-terminal truncated alpha-dystrobrevin-2 (65 kD).

26 ation of in vitro-translated proteins, alpha-dystrobrevin-2 binds dystrophin, whereas alpha-dystrobre

27 form-specific antibodies, we find that alpha-dystrobrevin-2 is localized on the sarcolemma and at the

28 alpha-Dystrobrevin-2 preferentially copurifies with dystrophin

29 alpha-Dystrobrevin-2 was lost from the nonsynaptic sarcolemma

30 not the closely related splice variant alpha-dystrobrevin-2.

31 of myopathy, despite reduced levels of alpha-dystrobrevin-2.

32 otein, physically interacts with DYB-1/alpha-dystrobrevin (a component of the dystrophin complex) and

33 Mice rendered null for alpha-dystrobrevin, a component of the dystrophin complex, hav

34 uscular junctions of mice deficient in alpha-dystrobrevin, a component of the dystrophin glycoprotein

35 In mice that lacked alpha-dystrobrevin, a component of the dystrophin-glycoprotein

36 e for the murine 87 kDa postsynaptic protein dystrobrevin, a dystrophin-associated protein.

37 Dystrobrevin, a dystrophin-related and -associated prote

38 in-associated protein complex (DPC) is alpha-dystrobrevin, a dystrophin-related and -associated prote

39 ere we describe the characterization of beta-dystrobrevin, a dystrophin-related protein that is abund

40 lecular associations and distribution of the dystrobrevins, a widely expressed family of dystrophin-a

41 , including dystroglycans, sarcoglycans, and dystrobrevins, along myofibers.

42 We show here that alpha-dystrobrevin (alpha-DB), a protein contributing to dystr

43 show that a cytoplasmic DGC component, alpha-dystrobrevin (alpha-DB), is dispensable for formation of

44 Da isoforms of tyrosine phosphorylated alpha-dystrobrevin (alpha-dbn) 1 (which are required for the m

45 nd immunoblotting assays, we show that alpha-dystrobrevin (alpha-dbn), an intracellular component of

46 alpha-syntrophin (alpha-syn) and alpha-dystrobrevin (alpha-dbn), two components of the dystroph

47 The dystrobrevins (alphaDB and betaDB) bind directly to dyst

48 igated the impact of the deficiency of alpha-dystrobrevin (alphadbn), a component of the DGC, on the

49 e also show that the interaction between the dystrobrevin and dystrophin coiled-coil domains is speci

50 ncodes a neuronal protein that binds to beta-dystrobrevin and may be part of the dystrophin protein c

51 omuscular junctions and interacts with alpha-dystrobrevin and that the level of alpha-catulin is redu

52 These results expand the role of dystrobrevin and the dystrophin complex in membrane sign

53 ystrophin complex in skeletal muscle: two on dystrobrevin and two on dystrophin or utrophin.

54 in complexes was examined by immunopurifying dystrobrevins and dystrophin.

55 adhesion components (e.g., catenin, coronin, dystrobrevin, and syndecan), consistent with its previou

56 ntified the dystrophin proteins, syntrophin, dystrobrevin, and utrophin as essential GPCR-interacting

57 Anti-dystrobrevin antibodies stain the sarcolemma in normal s

58 A beta-dystrobrevin antibody recognized a protein of the predic

59 ilarity in primary sequence, alpha- and beta-dystrobrevin are differentially distributed in the brain

60 ociated proteins, the sarcoglycans and alpha-dystrobrevin, are critical for both cardiac and skeletal

61 and the dystrophin homologues, utrophin and dystrobrevin, are restricted to the basolateral membrane

62 e postsynaptic membrane, and establish alpha-dystrobrevin as a key control point for regulation of mo

63 DAMAGE associates directly with alpha-dystrobrevin, as shown by yeast two-hybrid, and co-immun

64 We have identified a new dystrobrevin-associated protein, DAMAGE, that may play a

65 o-localizes with syntrophin, dystrophin, and dystrobrevin at skeletal muscle neuromuscular junctions.

66 muscular dystrophy patients, consistent with dystrobrevin being a dystrophin-associated protein.

67 Thus, like alpha-dystrobrevin, beta-dystrobrevin is likely to associate d

68 Since syntrophin and dystrobrevin bind to each other as well as to dystrophin

69 enome-wide linkage analysis on expression of dystrobrevin binding protein 1 (DTNBP1), a well-supporte

70 Deletion of dystrobrevin binding protein 1 has been linked to Herman

71 DTNBP1 (dystrobrevin binding protein 1) is a leading candidate s

72 DTNBP1 (dystrobrevin binding protein 1) remains a top candidate

73 Dysbindin-1 is best known as dystrobrevin-binding protein 1 (DTNBP1) and may thus be

74 The schizophrenia susceptibility gene dystrobrevin-binding protein 1 (DTNBP1) encodes dysbindi

75 association studies have recently implicated dystrobrevin-binding protein 1 (DTNBP1) in the etiology

76 ethyl transferase (COMT) and dysbindin (dys; dystrobrevin-binding protein 1 (DTNBP1))--implicated thr

77 In schizophrenia, the encoded protein dystrobrevin-binding protein 1 (dysbindin-1) is often re

78 polymorphisms within the 140-kb gene DTNBP1 (dystrobrevin-binding protein 1, or dysbindin) are strong

79 ween schizophrenia and the gene encoding the dystrobrevin-binding protein dysbindin.

80 in complex remains unclear, it is known that dystrobrevin binds directly to the syntrophins, a hetero

81 The C terminus of dystrobrevin binds specifically to the C terminus of dys

82 tation is dependent on the presence of alpha-dystrobrevin but not beta-dystrobrevin.

83 present study, we have cloned a novel alpha-dystrobrevin cDNA encoding a protein (referred to as alp

84 ma in normal skeletal muscle indicating that dystrobrevin co-localises with dystrophin and the dystro

85 In the brain, beta-dystrobrevin coimmunoprecipitates with the dystrophin is

86 ts, we propose a model in which a dystrophin-dystrobrevin complex is associated with two syntrophins.

87 Dystrobrevin complexes contain dystrophin and alpha1- an

88 ressed protein that binds to alpha- and beta-dystrobrevins, components of the dystrophin-associated p

89 Dystrobrevin coprecipitates with both the acetylcholine

90 alpha-Dystrobrevin (DB), a cytoplasmic component of the dystro

91 Our results show that dystrobrevin-deficiency is a generic feature of dystroph

92 e level of alpha-catulin is reduced in alpha-dystrobrevin-deficient mouse muscle.

93 t either the Torpedo 87 kDa protein or human dystrobrevin demonstrate that at least three of the spli

94 e protein in addition to a presumed distinct dystrobrevin, derived from an early duplication of an an

95 esent evidence for the heterodimerization of dystrobrevin directly with dystrophin.

96 tions in mouse skeletal muscle lacking alpha-dystrobrevin (Dtna(-/-)), we identified a highly signifi

97 odel of the DPC predicts that dystrophin and dystrobrevin each bind a single syntrophin molecule [3].

98 alpha- and beta-dystrobrevins failed to copurify with each other, howeve

99 Furthermore, beta-dystrobrevin forms a specific complex with dystrophin an

100 hese results demonstrate that syntrophin and dystrobrevin functionally associate with the DAP complex

101 ultiple loss-of-function (lf) mutants of the dystrobrevin gene dyb-1.dyb-1(lf) phenocopied slo-1(lf),

102 Alternative splicing of the alpha-dystrobrevin gene generates multiple isoforms which have

103 Dystrobrevin has two major isoforms, alpha and beta, wit

104 in, dystrophin-related protein-2 (DRP2), and dystrobrevin) have been described.

105 hippocampal formation sites lacking neuronal dystrobrevin (i.e., beta-dystrobrevin).

106 n regulating muscle Ca(2+) transients and of dystrobrevin in controlling neurotransmitter release and

107 and biochemical binding studies, that alpha-dystrobrevin in fact contains two independent syntrophin

108 eta-dystroglycan, alpha-syntrophin and alpha-dystrobrevin in mdx muscle.

109 The precise role of alpha-dystrobrevin in skeletal muscle has not yet been determi

110 eta1-, and beta2-syntrophin, dystrophin, and dystrobrevin, interact with Kir2 channels, as demonstrat

111 Dystrobrevin is a component of the dystrophin-associated

112 In skeletal muscle, alpha-dystrobrevin is a component of the dystrophin-associated

113 Alpha-dystrobrevin is a dystrophin-related protein expressed p

114 Dystrobrevin is a major component of a dystrophin-associ

115 alpha-Dystrobrevin is both a dystrophin homologue and a compon

116 beta-dystrobrevin is encoded by a 2.5-kb alternatively splice

117 interaction between alpha-catulin and alpha-dystrobrevin is evolutionarily conserved in C. elegans a

118 beta-Dystrobrevin is found in neurons and is highly enriched

119 In common with dystrophin, beta-dystrobrevin is found in neurons of the cortex and hippo

120 naptic AChEs are more stable, and that alpha-dystrobrevin is important for controlling the density an

121 Thus, like alpha-dystrobrevin, beta-dystrobrevin is likely to associate directly with dystro

122 ernatively spliced variants of the new alpha-dystrobrevin isoform, alpha-DB2b, are differentially exp

123 e amino acid differences in the CT region of dystrobrevin isoforms contribute to these differences.

124 It interacts with dystrobrevin isoforms differentially, with differences i

125 expression of exons 12 and 13 in other alpha-dystrobrevin isoforms in skeletal muscle and heart.

126 dystrophin and its interactions with the two dystrobrevin isoforms.

127 s contained varying ratios of syntrophin and dystrobrevin isoforms.

128 milar to that previously described for alpha-dystrobrevin isoforms.

129 Thus, alpha-dystrobrevin may serve a signaling function that is impo

130 By contrast, dystrobrevin membrane staining is severely reduced in mu

131 The tissue distribution of dystrobrevin mRNA shows five distinct transcripts which

132 with significant homology to the other known dystrobrevin (now termed alpha-dystrobrevin).

133 ntrinsic binding specificity for dystrophin, dystrobrevin, or utrophin, the observed preferential pai

134 Furthermore, alternative splicing of dystrobrevin provides a mechanism for regulating the sto

135 ver, the physiological function of the alpha-dystrobrevins remains unknown.

136 Analysis of the syntrophin-binding region of dystrobrevin reveals a tandem pair of predicted alpha he

137 Although the nature of dystrobrevin's association with the dystrophin glycoprot

138 To study alpha-dystrobrevin's function in skeletal muscle, we used the

139 Dystrophin and dystrobrevin stabilize the sarcolemma membrane by formin

140 Interestingly, dystrobrevin staining at the sarcolemma is dramatically

141 Normal dystrobrevin staining is observed in patients with other

142 Sequence alignments including this second dystrobrevin strongly support the concept that two disti

143 lycan engage in assembly with the dystrophin-dystrobrevin subcomplex through extensive interaction wi

144 These results suggest that members of the dystrobrevin subfamily form heterotypic associations wit

145 o-hybrid, and co-immunoprecipitates with the dystrobrevin-syntrophin complex from brain.

146 s of mice that lack dystrophin and Dp71, the dystrobrevin-syntrophin complexes are still formed, wher

147 ithin an alternatively spliced exon of alpha-dystrobrevin, termed the variable region-3 (vr3) sequenc

148 Control Dystrobrevin transcripts were detected equally from both

149 This domain interacts with both dystrobrevins, via their "leucine zipper" coiled-coil he

150 A positive interaction between DMN and alpha-dystrobrevin was confirmed with an in vitro coimmunoprec

151 To understand the role of syntrophin and dystrobrevin, we previously generated a series of transg

152 ins suggests association with dystrophin and dystrobrevin, whereas all three syntrophins could potent

153 the possibility that pairing of a particular dystrobrevin with dystrophin may be regulated, thereby p

154 e 2p22-23 that encodes a novel protein, beta-dystrobrevin, with significant homology to the other kno