ライフサイエンスコーパス: Dsg2

1 zheimer's disease risk factor, desmoglein 2 (DSG2).

2 he epithelial junction protein desmoglein 2 (DSG2).

3 ngle known desmosomal protein, Desmoglein 2 (Dsg2).

4 to highly conserved residues within PKP2 and DSG2.

5 but not PG(WT) to desmosome proteins DSP and DSG2.

6 ructural details of the Ad3 interaction with DSG2.

7 g2 cleavage product and internalized pool of Dsg2.

8 nerated an antibody, AH12.2, that recognizes Dsg2.

9 e pair of desmosomal glycoproteins, Dsc2 and Dsg2.

10 hr170) are required for the translocation of Dsg2.

11 n the subcellular distribution of endogenous Dsg2.

12 of activated p38 MAPK with Dsg3 but not with Dsg2.

13 ually, ablated or reduced Ad knob binding to DSG2.

14 which might facilitate the interaction with DSG2.

15 identify variants with increased affinity to DSG2.

16 alizes to lipid rafts along with full-length Dsg2.

17 n tumors from transgenic mice overexpressing Dsg2.

18 ith the C-terminal fragment of desmoglein 2 (Dsg2), a desmosomal cadherin often overexpressed in mali

19 sion levels of 2 genes as the primary genes: DSG2, a desmosomal cadherin involved in Wnt/beta-catenin

20 ce were prepared with cardiomyocyte-specific DSG2 ablation.

21 However, the mechanisms by which Dsg2 activates these signaling pathways and the relative

22 Mice carrying 2 mutant DSG2 alleles coding for Dsg2 lacking part of the adhesiv

23 Interaction with DSG2 allows the virus not only to enter cells but also t

24 istribution was paralleled by an increase in Dsg2 and desmoplakin in the Triton-insoluble cell fracti

25 s demonstrate that the desmosomal cadherins, Dsg2 and Dsc1a, are involved in a direct Ca2+-dependent

26 rotein E-cadherin and the desmosome proteins DSG2 and DSC2 are important for aggregation.

27 We demonstrate that Dsg2 and Dsc2 both exhibit microtubule-dependent transpo

28 emonstrate that partner desmosomal cadherins Dsg2 and Dsc2 play opposing roles in controlling colonic

29 Mutations in DSP, JUP, PKP2, DSG2 and DSC2, encoding desmosomal proteins desmoplakin,

30 Crystal structures of ectodomains from Dsg2 and Dsg3 and from Dsc1 and Dsc2 show binding throug

31 n this study, we compared the involvement of Dsg2 and Dsg3 in the p38 MAPK-dependent regulation of ke

32 , PKI166 blocked tyrosine phosphorylation of Dsg2 and plakoglobin following epidermal growth factor s

33 ion of the desmosomal cadherin desmoglein-2 (Dsg2) and characterized the role that palmitoylation of

34 red the assembly properties of desmoglein 2 (Dsg2) and desmocollin 2 (Dsc2), which are widely express

35 The accumulated levels of desmoglein 2 (Dsg2) and desmocollin 2 increased 1.7-2.0-fold, and both

36 ne desmosomal cadherins termed desmoglein-2 (Dsg2) and desmocollin-2 (Dsc2) that affiliate with the u

37 oglobin, plakophilin 2 (PKP2), desmoglein 2 (DSG2), and desmocollin 2 (DSC2), respectively, cause ARV

38 calized to the N-terminal regions of DSP and DSG2, and localized to highly conserved residues within

39 bands has compound-heterozygous mutations in DSG2, and the remaining three have isolated heterozygous

40 d CD46, structural details for Ad binding to DSG2 are still elusive.

41 Desmocollin-2 (Dsc2) and desmoglein-2 (Dsg2) are transmembrane cell adhesion proteins of desmos

42 oviruses use the epithelial junction protein DSG2 as a receptor for infection and lateral spread.

43 he epithelial junction protein desmoglein 2 (DSG2) as a receptor for infection.

44 uman adenoviruses (HAdVs) uses desmoglein 2 (DSG2) as a receptor for infection.

45 Recently, we identified desmoglein 2 (DSG2) as the main receptor for a group of species B aden

46 A proteomic screen for Dsg2-associated proteins in intestinal epithelial cells

47 In this study we show that Dsg2 associates with caveolin-1 (Cav-1), the major prote

48 ere, we show that EGFR inhibition stabilizes Dsg2 at intercellular junctions by interfering with its

49 per, we show that the DUR of Dsg2 stabilized Dsg2 at the cell surface by inhibiting its internalizati

50 on of the desmosomal cadherin, desmoglein 2 (Dsg2), at cell-cell interfaces accompanied by inhibition

51 We show that Dsg2 but not another desmosomal cadherin, Dsc2, is cleav

52 , blocked shedding and depleted internalized Dsg2, but less so E-cadherin, in highly invasive SCC68 c

53 m sera of patients with SCC were enriched in Dsg2 C-terminal fragment and epidermal growth factor rec

54 M10 siRNA enhanced accumulation of a 100-kDa Dsg2 cleavage product and internalized pool of Dsg2.

55 delayed, and a pool of the non-palmitoylated Dsg2 co-localized with lysosomal markers.

56 ane in Dsg3 knockout cells, we conclude that Dsg2 compensates for Dsg3 loss of function.

57 We propose that loss of Dsg2 compromises adhesion, and that this is a major path

58 The genetic DSG2 constellations encountered are compatible with loss

59 Sequence analysis revealed that Dsg2 contains a putative Cav-1-binding motif.

60 We report that mutations in DSG2 contribute to the development of ARVD/C.

61 t competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epi

62 Dsg2-deficient cells demonstrated a compensatory increas

63 iated loss of Dsc2 restored proliferation in Dsg2-deficient cells.

64 Dsg2 transport, resulting in the assembly of Dsg2-deficient junctions with minimal impact on distribu

65 ol cells, the response to MMP-inhibition was Dsg2-dependent.

66 ess, because subsequent targeting of Dsg3 in Dsg2-depleted cells led to drastically enhanced keratino

67 chanisms, we examined whether heart-specific Dsg2 depletion triggers cardiomyopathy.

68 cancer cell lines, JO-1 mediated cleavage of DSG2 dimers and activated intracellular signaling pathwa

69 mbling the Cav-1 scaffolding domain bound to Dsg2, disrupted normal Dsg2 staining and interfered with

70 The shed DSG2 domain can be detected in cell culture supernatant

71 Dsg2 downregulation inhibited epidermal growth factor re

72 coding exons/splice junctions of PKP2, DSP, DSG2, DSC2, and TMEM43 were genotyped for 93 probands di

73 alloprotease (MMP)-dependent shedding of the Dsg2 ectodomain and tyrosine phosphorylation of its cyto

74 , BIN1, CASS4, CD33, CD2AP, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB5-DBR1, INPP5D, MS4A, MEF2C,

75 This study defines a mechanism by which Dsg2 expression in cancer cells can modulate the tumor m

76 Gal3 bound to N-linked beta-galactosides in Dsg2 extracellular domain and co-sedimented with caveoli

77 dividuals had mutations in PKP2, DSP, and/or DSG2 genes.

78 When cocultured with Dsg2/green fluorescence protein-expressing SCC cells, gr

79 These mice expressed human DSG2 (hDSG2) at a level and in a pattern similar to thos

80 acellular domain of DSG2, thereby disrupting DSG2 homodimers between epithelial cells.

81 Dsc2 and Dsg2 IFs were stronger in superficial layers, but Dsc3 a

82 Knockdown of DSG2 in APOE varepsilon3/4 induced neurons effectively r

83 6001 resulted in accumulation of full-length Dsg2 in EVs and reduced EV release.

84 Overexpression of Dsg2 increased EV release and mitogenic content includin

85 We found that the DSG2-interacting domain(s) within Ad3 is formed by sever

86 inical symptoms associated with infection by DSG2-interacting HAdVs and provide a rationale for using

87 We confirmed this pathway with a second DSG2-interacting serotype, Ad14, and its recently emerge

88 his structure reveals that the ectodomain of Dsg2 is flexible even in the calcium-bound state and, on

89 We have shown previously that Dsg2 is less important for keratinocyte cohesion compare

90 00 solubility assays demonstrate that mutant Dsg2 is more soluble than wild-type protein.

91 The observations show that the presence of Dsg2 is not essential for late heart morphogenesis and f

92 Additionally, we observed that Dsg2 is proteolytically processed; resulting in a 95-kDa

93 Desmoglein-2 (Dsg2) is a desmosomal cadherin that is aberrantly expres

94 We recently discovered that desmoglein 2 (DSG2) is a receptor for human adenovirus species B serot

95 ning pool revealed that Dsg3, in contrast to Dsg2, is present in relevant amounts in the unbound pool

96 Because DSG2 knockouts die during early embryogenesis, mice were

97 ce carrying 2 mutant DSG2 alleles coding for Dsg2 lacking part of the adhesive EC1-EC2 domains presen

98 Although mutant Dsg2 localizes to endogenous desmosomes, there is a sign

99 The desmosomal cadherin desmoglein 2 (Dsg2) localizes to the intercalated disc coupling adjace

100 nerated transgenic mice containing the human DSG2 locus.

101 urther delineate the mechanism that leads to DSG2-mediated epithelial junction opening in cells expos

102 We also show that a Dsg2 mutant, V977fsX1006, identified in arrhythmogenic r

103 Desmoglein 2 gene (DSG2) mutations cause arrhythmogenic cardiomyopathy (AC)

104 Dsc2.myc and Dsg2.myc assembled efficiently into desmosomes in every

105 of 198 subjects (7%), including DSP (n = 4), DSG2 (n = 5), DSC2 (n = 3), and junctional plakoglobin (

106 ing desmoplakin (DSP) (n = 6), desmoglein-2 (DSG2) (n = 5), plakophilin-4 (PKP4) (n = 1), and desmoco

107 nificantly change the fiber knob affinity to DSG2 or the intracellular signaling and DSG2 shedding in

108 a cells from patients with mutations in DSP, DSG2, or DSC2 but not in PKP2 or JUP.

109 haracterized the role that palmitoylation of Dsg2 plays in its localization and stability in cultured

110 ADAM9 and 15 silencing also impaired Dsg2 processing, supporting the idea that this desmosoma

111 interfering RNA-mediated down-regulation of Dsg2 protected epithelial cells from apoptosis.

112 Dsg2 protein expression was reduced below 3% in the hear

113 f human colon cancers demonstrated increased Dsg2 protein expression.

114 e possibility that accumulation of truncated Dsg2 protein interferes with desmosome assembly and/or m

115 nal fragment of Dsg2 regulates apoptosis and Dsg2 protein levels.

116 The increase in Dsg2 protein was in part due to the inhibition of matrix

117 In the absence of functional Gal3, Dsg2 protein was internalized from the plasma membrane a

118 Interestingly, Dsg2 proteolytic products are elevated in vivo in skin t

119 ver, we report that a C-terminal fragment of Dsg2 regulates apoptosis and Dsg2 protein levels.

120 studies highlight a novel mechanism by which Dsg2 regulates IEC apoptosis driven by cysteine protease

121 mediating intercellular desmosomal adhesion, Dsg2 regulates mitogenic signaling that may promote canc

122 r, these data suggest that palmitoylation of Dsg2 regulates protein transport to the plasma membrane.

123 that this is a major pathogenic mechanism in DSG2-related and probably other desmosome-related ACs.

124 e blood were significantly different: EPDR1, DSG2, SCD5, P2RY5, MGAT5, RHOQ, UCHL1, ZNF652, RALGPS2,

125 y to DSG2 or the intracellular signaling and DSG2 shedding in epithelial cancer cells.

126 Furthermore, in contrast to depletion of Dsg2, siRNA-mediated silencing of Dsg3 induced p38 MAPK

127 In this paper, we show that the DUR of Dsg2 stabilized Dsg2 at the cell surface by inhibiting i

128 lding domain bound to Dsg2, disrupted normal Dsg2 staining and interfered with the integrity of epith

129 The Dsg2 structure has an excellent fit with the electron to

130 Forced dimerization of a Dsg2 tail lacking the DUR led to decreased internalizati

131 ar cardiomyopathy patients, led to a loss of Dsg2 tail self-association and underwent rapid endocytos

132 in turn, cleaves the extracellular domain of DSG2 that links epithelial cells together.

133 the Ad3 knob that resulted in affinities to DSG2 that were several orders of magnitude higher than t

134 xtamembrane (intracellular anchor) domain of Dsg2 that, when mutated, eliminate its palmitoylation.

135 ntestinal desmosomal cadherin, desmoglein-2 (Dsg2) that pairs with Dsc2, results in decreased epithel

136 the cleavage of the extracellular domain of DSG2, thereby disrupting DSG2 homodimers between epithel

137 Interestingly, trafficking of the mutant Dsg2 to the cell surface was delayed, and a pool of the

138 Disruption of lipid rafts shifted Dsg2 to the non-raft fractions, leading to the accumulat

139 asma membrane accumulation without affecting Dsg2 trafficking.

140 nctional interference with kinesin-1 blocked Dsg2 transport, resulting in the assembly of Dsg2-defici

141 yses that Ad3-K/S/Kn, through its binding to DSG2, triggered the transient opening of intercellular j

142 Ad3 binding to DSG2 triggers the transient opening of epithelial juncti

143 odomain of desmosomal cadherin desmoglein 2 (Dsg2), using a combination of small-angle X-ray scatteri

144 cally enhanced keratinocyte dissociation and Dsg2 was enhanced at the membrane in Dsg3 knockout cells

145 In vivo, Dsg2 was highly up-regulated in the head and neck SCCs,

146 s junctions, whereas only a minor portion of Dsg2 was seen in these areas in the parental cells.

147 eins, desmocollin 2 (Dsc2) and desmoglein 2 (Dsg2) were expressed throughout, but Dsc3 and Dsg3 were

148 probands with ARVD/C caused by mutations in DSG2, which encodes desmoglein-2, a component of the car

149 Furthermore, the association of Dsg2 with Cav-1 may provide a mechanism for regulating m

150 Ad3-K/S/Kn bound to DSG2 with high affinity and blocked Ad3 infection.

151 Ad3 binds to DSG2 with its fiber knob domain and triggers intracellul

152 Inhibiting ectodomain shedding of Dsg2 with the matrix metalloproteinase inhibitor GM6001