ライフサイエンスコーパス: myotubularin

1 thy, and Sbf1, a newly isolated homologue of myotubularin.

2 used by deficiency of the lipid phosphatase, myotubularin.

3 d to introduce the p.R69C missense change in myotubularin.

4 odes the phosphoinositide lipid phosphatase, myotubularin.

5 used by deficiency of the lipid phosphatase, myotubularin.

6 used by deficiency of the lipid phosphatase, myotubularin.

7 congenital myopathy caused by deficiency of myotubularin.

8 -specific phosphatases that include PTEN and myotubularin.

9 omeric complexes with catalytically inactive myotubularins.

10 F2 belong to a family of proteins called the myotubularins.

11 most severe form, X-linked CNM, is caused by myotubularin 1 (MTM1) loss-of-function mutations, while

12 f1 shares extensive sequence similarity with myotubularin, a dual specificity phosphatase (dsPTPase)

13 We report here that myotubularin, a protein tyrosine phosphatase required fo

14 Recently, myotubularin, a second PTP superfamily enzyme associated

15 Myotubularins, a large family of catalytically active an

16 e mutation is present, which provides enough myotubularin activity to account for the relatively mild

17 ne encoding the ubiquitous lipid phosphatase myotubularin, an enzyme specifically dephosphorylating p

18 l expression and subcellular localization of myotubularin and MTMR2 are differentially regulated, res

19 lipid phosphatase activities of recombinant myotubularin and MTMR2 demonstrates that their enzymatic

20 In addition, myotubularin and MTMR2 enhanced green fluorescent protei

21 To this end, we have analyzed myotubularin and MTMR2 transcripts during induced differ

22 Myotubularin and myotubularin-related proteins are evolu

23 dissect the functions of the MTM1 and MTMR2 myotubularins and establish how they contribute to endos

24 Complex formation between the active myotubularins and MTMR9 increases their catalytic activi

25 Myotubularins are a family of dual-specificity phosphata

26 The myotubularins are a large family of inositol polyphospha

27 Mutations in several myotubularins are associated with human disease.

28 Although several myotubularins are known to regulate phosphoinositide-pho

29 Myotubularins are phosphoinositide (PI) 3-phosphatases t

30 Interestingly, nearly half of the metazoan myotubularins are predicted to be catalytically inactive

31 Mutations in worm MTM-6 and MTM-9, myotubularins belonging to two subgroups, disorganize ph

32 We further demonstrate that direct myotubularin binding to the type III PI 3-kinase complex

33 Finally, we provide evidence that myotubularin, but not MTMR2, can modulate the levels of

34 Mutations in the MTM1 gene encoding myotubularin cause X-linked myotubular myopathy (XLMTM),

35 ular myopathy mouse model (knock-out for the myotubularin coding gene Mtm1) that a down-regulated myo

36 Instead, myotubularin deficiency is associated with altered toler

37 ubularin-deficient muscle, but the impact of myotubularin deficiency on myogenic stem cells within mu

38 may relate to the progression of disease in myotubularin deficiency, and may also be used to develop

39 trophy can attenuate symptoms resulting from myotubularin deficiency, the effect of ActRIIB-mFC treat

40 ctively, due to differences in the degree of myotubularin deficiency.

41 ctive treatment for the weakness observed in myotubularin deficiency.

42 size would cause symptomatic improvement in myotubularin deficiency.

43 t of ActRIIB-mFC treatment was determined in myotubularin-deficient (Mtm1delta4) mice.

44 ivation and downstream survival signaling in myotubularin-deficient cells is caused by accumulation o

45 ion factors is also significantly reduced in myotubularin-deficient cells.

46 ained from severely symptomatic (Mtm1delta4) myotubularin-deficient mice.

47 type-phenotype correlation data to develop a myotubularin-deficient mouse model with a less severe ph

48 +) release is spatially heterogeneous within myotubularin-deficient muscle fibers, with focally defec

49 tructural and physiological abnormalities in myotubularin-deficient muscle, but the impact of myotubu

50 response to dehydration stress, and the two myotubularins differentially affect the Arabidopsis dehy

51 ease through siRNA-mediated depletion of the myotubularins, excess PI(3)P accumulates on early (MTM1)

52 Our findings provide evidence that myotubularin exerts its effects during myogenesis by reg

53 de evidence that siRNA-mediated silencing of myotubularin expression markedly inhibits growth factor-

54 ll serve as a model for other members of the myotubularin family and provide a framework for understa

55 Mutations in members of the myotubularin family cause the human neuromuscular disord

56 The myotubularin family consists of 16 different proteins, 9

57 ivity toward this substrate is common to all myotubularin family enzymes.

58 sting that this activity is intrinsic to all myotubularin family members.

59 MTMR2 encodes a member of the myotubularin family of phosphoinositide-3-phosphatases,

60 also reveals that the GRAM domain, found in myotubularin family phosphatases and predicted to occur

61 nd implicate signaling pathways regulated by myotubularin family proteins in spermatogenesis and germ

62 e here that Sbf1, a pseudophosphatase of the myotubularin family, is expressed at high levels in semi

63 codes a large, uncharacterized member of the myotubularin family.

64 While loss of myotubularin function causes severe disease phenotypes i

65 pendent growth/survival cues due to impaired myotubularin function may be a critical factor underlyin

66 The myotubularin gene, MTM1, is mutated in the genetic disor

67 g of 92% of the known coding sequence of the myotubularin gene.

68 nd proliferated in the basal metazoan group, myotubularin genes are not found in the unicellular rela

69 Both active and inactive myotubularins have essential functions in mammals and in

70 le structural conservation, plant and animal myotubularins have significantly diverged in their funct

71 demonstrating that PI(3)P is a substrate for myotubularin in vivo.

72 We studied a subfamily of homologous myotubularins, including myotubularin-related protein 6

73 Both Sbf1 and myotubularin interact with the SET domains of Hrx and ot

74 A candidate gene, myotubularin, involved in the pathogenesis of X-linked m

75 Myotubularin is a 3-phosphoinositide phosphatase that is

76 Myotubularin is the archetype of a family of highly cons

77 scles from Mtm1delta4 mice, which produce no myotubularin, is markedly impaired.

78 Saccharomyces cerevisiae strain in which the myotubularin-like gene (YJR110w) is disrupted also exhib

79 The myotubularin (MTM) family constitutes one of the most hi

80 MR6) is a catalytically active member of the myotubularin (MTM) family, which is composed of 14 prote

81 related protein 7 (MTMR7) is a member of the myotubularin (MTM) family.

82 The family of disease-related myotubularin (MTM) phosphoinositide phosphatases include

83 We identified myotubularin (mtm), a Drosophila melanogaster MTM1/MTMR2

84 Myotubularins (MTM) are a large subfamily of lipid phosp

85 encoding the phosphoinositide 3-phosphatase myotubularin (MTM1) are responsible for a pediatric dise

86 s-of-function mutations in the gene encoding myotubularin (MTM1) result in X-linked CNM (XLCNM, also

87 NM, is caused by mutations in MTM1, encoding myotubularin (MTM1), a lipid phosphatase.

88 hy, is due to mutations in the gene encoding myotubularin (MTM1), while mutations in dynamin 2 (DNM2)

89 hy (XLMTM)-associated PtdIns(3)P phosphatase myotubularin (MTM1).

90 Myotubularins (MTMs) belong to a large subfamily of phos

91 Myotubularins (MTMs) constitute a large family of lipid

92 a catalytically inactive substrate-trapping myotubularin mutant (C375S) in human 293 cells increases

93 RNAi of the dual-specificity phosphatase, Myotubularin, or the related Sbf "antiphosphatase" resul

94 ether, this study demonstrated that Ymr1p, a myotubularin phosphatase family member, functions in the

95 and provide insight into the specificity of myotubularin phosphatases toward phosphoinositide substr

96 here genes encoding both active and inactive myotubularins (phosphoinositide 3-phosphatases) have app

97 Catalytically active myotubularins possess 3-phosphatase activity dephosphory

98 Myotubularin protein is undetectably low because the int

99 Myotubularin protein levels and localization were abnorm

100 ing findings suggest that even low levels of myotubularin protein replacement can improve the muscle

101 nts within the active, but not the inactive, myotubularins provides insight into the functional diffe

102 gs are significant because they suggest that myotubularin regulates Akt activation via a cellular poo

103 actor 2 mutation, 1 a periaxin mutation, 0 a myotubularin related protein 2 mutation, 1 a neurofilame

104 2, early growth response factor 2, periaxin, myotubularin related protein 2, N-myc downstream regulat

105 arget pre-mRNAs, cardiac troponin T (Tnnt2), myotubularin-related 1 gene (Mtmr1) and the muscle-speci

106 by recessively inherited mutations in either myotubularin-related 2 (MTMR2) or MTMR13 (also called SE

107 Associations of down-regulation of myotubularin-related phosphatase 1 (a phosphoinositide 3

108 autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negativ

109 P]-mediated signaling, the role of the yeast myotubularin-related PI(3)P phosphatase Ymr1p was invest

110 oles are played by PP1 with tyrosine PPs and Myotubularin-related PPs having significant roles in reg

111 oth the recombinant yeast enzyme and a human myotubularin-related protein (KIAA0371) are able to deph

112 concentrated on two lipid phosphatases, the myotubularin-related protein (MTMR)9 and -7.

113 s-of-function mutations in the gene encoding myotubularin-related protein 2 (MTMR2) cause Charcot-Mar

114 Alterations in the myotubularin-related protein 2 (MTMR2) gene on chromosom

115 CMT4B results from mutations in either myotubularin-related protein 2 (MTMR2; CMT4B1) or MTMR13

116 B is caused by recessive mutations in either myotubularin-related protein 2 (MTMR2; CMT4B1) or MTMR13

117 e identified a previously undefined role for myotubularin-related protein 3 (MTMR3) in amplifying PRR

118 Myotubularin-related protein 6 (MTMR6) is a catalyticall

119 In contrast, mRNA expression of myotubularin-related protein 6 (MTMR6), a negative regul

120 )P] for channel activity and is inhibited by myotubularin-related protein 6 (MTMR6), a PI(3)P phospha

121 amily of homologous myotubularins, including myotubularin-related protein 6 (MTMR6), MTMR7, and MTMR8

122 n and is inhibited by the PI(3)P phosphatase myotubularin-related protein 6 (MTMR6).

123 Myotubularin-related protein 7 (MTMR7) is a member of th

124 eromer with an enzymatically inactive member myotubularin-related protein 9 (MTMR9), both in vitro an

125 We demonstrate here that the myotubularin-related protein MTMR2, which is mutated in

126 -exchange mass spectrometry studies of human myotubularin-related protein-2 (MTMR2) in complex with p

127 ations occurring in the gene MTMR2, encoding myotubularin-related protein-2, a dual specificity phosp

128 Myotubularin-related proteins are a large subfamily of p

129 Myotubularin and myotubularin-related proteins are evolutionarily conserv

130 Thus, myotubularin-related proteins have a role in controlling

131 In contrast with myotubularin, Sbf1 lacks a functional catalytic domain w

132 p.R69C mice, which produce small amounts of myotubularin, showed impaired contractile function only

133 Myotubularin silencing also inhibits Akt-dependent signa

134 Recombinant human myotubularin specifically dephosphorylates PI(3)P in vit

135 These include myotubularin, the gene of which is mutated in a subset o

136 c regulated recruitment of the 3-phosphatase myotubularin to endosomal membranes in intact cells.

137 t mRNAs, leading to premature termination of myotubularin translation.

138 We conclude that myotubularin-type phosphatases link SET-domain containin

139 We and others have previously shown that myotubularin utilizes the lipid second messenger, phosph

140 Short-term replacement of myotubularin with a prototypical targeted protein replac