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 presence of alpha-dystrobrevin but not beta-dystrobrevin.

6 omponents of the DAP complex, syntrophin and dystrobrevin.

7 played normal localization of syntrophin and dystrobrevin.

8 nd its relationship to the distantly related dystrobrevins.

9 tinct properties of association on the alpha-dystrobrevins.

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

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

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

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

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

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

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

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

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

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

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

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

22 -1(lf) were partially rescued by mouse alpha-dystrobrevin-1.

23 1 (84 kD), and COOH-terminal truncated alpha-dystrobrevin-2 (65 kD).

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

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

26 alpha-Dystrobrevin-2 preferentially copurifies with dystrophin

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

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

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

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

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

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

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

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

35 Dystrobrevin, a dystrophin-related and -associated prote

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

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

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

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

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

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

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

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

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

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

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

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

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

49 in complexes was examined by immunopurifying dystrobrevins and dystrophin.

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

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

52 Anti-dystrobrevin antibodies stain the sarcolemma in normal s

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

81 Dystrobrevin complexes contain dystrophin and alpha1- an

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

83 Dystrobrevin coprecipitates with both the acetylcholine

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

104 Dystrobrevin is a component of the dystrophin-associated

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

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

107 Dystrobrevin is a major component of a dystrophin-associ

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

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

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

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

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

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

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

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

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

117 s contained varying ratios of syntrophin and dystrobrevin isoforms.

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

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

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

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

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

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

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

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

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

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

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

129 Interestingly, dystrobrevin staining at the sarcolemma is dramatically

130 Normal dystrobrevin staining is observed in patients with other

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

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

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

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

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

136 Control Dystrobrevin transcripts were detected equally from both

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

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

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

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

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

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