ライフサイエンスコーパス: Ano1

1 eticulum-associated, proteasomal turnover of ANO1.

2 ess mRNA for a previously unknown variant of Ano1.

3 lower kinetics compared with the full-length Ano1.

4 nts to determine the quaternary structure of Ano1.

5 e first to probe the quaternary structure of Ano1.

6 ntracellular trafficking, or localization of ANO1.

7 dy of the structure-function relationship of ANO1.

8 ICC express ANO1, a Ca(2+)-activated Cl(-) channel.

9 ANO1, a calcium-activated chloride channel, is highly ex

10 , yet our understanding of the mechanisms of ANO1 activation and regulation are only beginning to eme

11 oupling may represent a general mechanism of ANO1 activation in native tissues.

12 serves as an adjunct to other mechanisms of ANO1 activation.

13 sensitivity of ANO1 and hence in regulating ANO1 activation.

14 ation, we used pharmacological inhibitors of Ano1 activity and shRNA-mediated knock down of Ano1 expr

15 echanism of channel gating and regulation of ANO1 activity.

16 tivated chloride channel (CaCC) anoctamin 1 (ANO1, also known as TMEM16A).

17 Knockdown of ANO1 in ANO1-amplified breast cancer cell lines and other cancer

18 targeting approach for antitumor therapy in ANO1-amplified cancers.

19 bitor CaCCinh-A01 decreases proliferation of ANO1-amplified cell lines; however, the mechanism of act

20 Ano1 and Cacna1c expression levels were examined by quan

21 and tone in the IAS were nearly abolished by ANO1 and CavL antagonists.

22 We propose that ANO1 and CavL collaborate to generate SWs in ICC-IM foll

23 ane potential and contraction indicated that ANO1 and CavL have a central role in SW generation, phas

24 These data support a central role for ANO1 and CavL in the generation of SWs and tone in the I

25 Ion selectivity of CFTR, ANO1 and GlyR is critically affected by the electric per

26 rbonate permeability (P HC O3/ Cl ) of CFTR, ANO1 and GlyR.

27 coupling calcium and voltage sensitivity of ANO1 and hence in regulating ANO1 activation.

28 or a better understanding of the function of ANO1 and its role in health and diseases.

29 tivity of some anion channels, such as CFTR, ANO1 and the glycine receptor (GlyR), by changing pore s

30 IM were the predominant cell type expressing ANO1 and the most likely candidate for SW generation.

31 Recently, TMEM16A (ANO1) and -B were shown to be critical components of CaC

32 s to be functionally characterized, TMEM16A (ANO1) and TMEM16B (ANO2), form Ca(2+)-activated Cl(-) ch

33 -activated Cl(-) channels (ANO1, encoded by Ano1) and voltage-dependent L-type Ca(2+) channels (CavL

34 Ca(2+) -activated Cl(-) channels (encoded by Ano1) and voltage-dependent L-type Ca(2+) channels (enco

35 By analyzing ANO1-ANO6 chimeric proteins, we identify a domain in ANO

36 ANO1 antagonists also abolished SWs as well as transient

37 scles, and the sensitivity of contraction to ANO1 antagonists was the same in stretched versus un-str

38 Several transcripts for Ano1 are generated by alternative splicing of four exons

39 ver, the mechanisms underlying regulation of Ano1 are unknown.

40 th 11q13 amplification, thereby establishing ANO1 as a promising target for therapy in these highly p

41 We find that Ano1 associates with the signaling/scaffolding proteins

42 co-localize with other ICC markers CD34 and Ano1, but not with mast cell marker tryptase.

43 es provide new perspectives on regulation of Ano1 by Ca2+.

44 y modulate the anion selectivity of CFTR and ANO1 by changing the pore size.

45 he activity of the CaCC TMEM16A/Anoctamin 1 (ANO1) by directly engaging the channel at the cell surfa

46 Ano1, Cacna1c and Kit gene expression were the same in e

47 reased ANO1 calcium sensitivity and rendered ANO1 calcium gating voltage-independent, demonstrating a

48 Mutations such as S741T increased ANO1 calcium sensitivity and rendered ANO1 calcium gatin

49 Ano1 can be gated by Ca(2+) or by voltage in the absence

50 ometric protein networks associated with the Ano1 channel.

51 These are similar in conductance to ANO1 channels (8 pS) expressed in HEK293 cells.

52 Recent findings indeed indicate that ANO1 channels often co-localize with sources of intracel

53 Recent findings indeed indicate that ANO1 channels often co-localize with sources of intracel

54 intracellular Ca(2+) transients towards the ANO1 channels.

55 us intracellular Ca2+ transients towards the ANO1 channels.

56 Moreover, ANO1 chloride channel activity was important for cell vi

57 Our results highlight the involvement of the ANO1 chloride channel in tumor progression and provide i

58 pid-interacting proteins are enriched in the Ano1 complex.

59 Thus, utilizing mCherry- and eGFP-tagged Ano1 constructs, we conducted biochemical and Forster re

60 Amplification of ANO1 correlated with disease grade and poor prognosis.

61 oreover, interfering RNA for moesin modifies Ano1 current without affecting its surface expression le

62 C-IM are the probable cellular candidate for ANO1 currents and SW generation.

63 ANO1 protein levels in these cells, whereas ANO1 currents were still inhibited by CaCCinh-A01, indic

64 to describe inhibitors capable of promoting ANO1 degradation and report new inhibitors of ANO1-depen

65 not sufficient to diminish proliferation of ANO1-dependent cancer cells.

66 ctivity of ANO1 is not sufficient to inhibit ANO1-dependent cell proliferation, indicating that the r

67 NO1 degradation and report new inhibitors of ANO1-dependent cell proliferation.

68 Loss of function of ANO1 did not inhibit the development of ICC networks tha

69 ydryl reagents alter the Ca2+ sensitivity of Ano1 E702C and E705C as expected if E702 and E705 are in

70 ANO1 expression was examined in wildtype and Ano1(/+egfp) mice with immunohistochemical techniques.

71 unction of a new class of CaCC, anoctamin 1 (ANO1), encoded by Tmem16a, which was discovered to be hi

72 ivation of Ca(2+) -activated Cl(-) channels (ANO1, encoded by Ano1) and voltage-dependent L-type Ca(2

73 romobility shift assays, which revealed that Ano1 exists as a dimer.

74 Knockdown of ANO1 expression caused decreased insulin secretion in hu

75 Dual labelling revealed that ANO1 expression could be resolved in ICC but not smooth

76 Changes in Ano1 expression in ICC may directly contribute to diabet

77 o1 activity and shRNA-mediated knock down of Ano1 expression in organotypic cultures of Ano1 WT small

78 o glucose, this contact was strengthened and ANO1 expression increased, whereas inhibition of INS gen

79 While ANO1 expression negatively correlates with survival in s

80 ed with fluorescence-activated cell sorting, Ano1 expression was 26.5-fold greater in ICC than in SMC

81 ANO1 expression was examined in wildtype and Ano1(/+egfp

82 t feedback loop involving INS transcription, ANO1 expression, and insulin secretion.

83 Treatment with a known regulator of Ano1 expression, IL-4, increased promoter activity by 1.

84 found three CpG islands that correlated with ANO1 expression, including two positively correlated wit

85 on by INS promoter targeting siRNA decreased ANO1 expression, revealing a regulatory effect of INS pr

86 rrelated with but not sufficient to increase ANO1 expression, suggesting methylation of positively co

87 aling a regulatory effect of INS promoter on ANO1 expression.

88 ositively correlated CpG islands potentiates ANO1 expression.

89 ly correlated CpG island without a change in ANO1 expression.

90 Ano1, ezrin, and moesin/radixin colocalize apically in s

91 ized information about mechanisms regulating Ano1 function and trafficking to polarized domains of th

92 haracteristics, providing new tools to study ANO1 function in biological systems, paving the path for

93 We show that inhibition of ANO1 function is not sufficient to diminish proliferatio

94 TMEM16A (ANO1) functions as a calcium-activated chloride channel

95 d Tmem16) superfamily, but the mechanisms of Ano1 gating by Ca2+ remain enigmatic.

96 anscripts encoded by alternative splicing of Ano1 gene in gastric muscles of patients with diabetic g

97 gion near the insulin (INS) promoter and the ANO1 gene, lying 68 Mb away on human chromosome 11, whic

98 In conclusion, Ano1 has a previously unidentified role in the regulatio

99 dependent chloride channel TMEM16A (TAOS2 or ANO1) has been reported in several malignancies.

100 Knockdown of ANO1 in ANO1-amplified breast cancer cell lines and othe

101 l proliferation, indicating that the role of ANO1 in cancer only partially depends on its function as

102 lial cells, and overexpression of moesin and Ano1 in HEK cells alters the subcellular localization of

103 Overexpression of Ano1 in HEK cells or Xenopus oocytes is sufficient to ge

104 To explore a possible role of ANO1 in insulin metabolism, we carried out experiments i

105 Genetic deletion of Ano1 in mice resulted in loss of slow waves in smooth mu

106 ortant changes in expression and splicing of Ano1 in patients with diabetic gastroparesis that alter

107 ws deeper understanding of the regulation of Ano1 in physiology and as a potential therapeutic target

108 ese data demonstrate the fundamental role of ANO1 in the generation of slow waves in GI ICC.

109 To confirm the role of Ano1 in the loss of Ca(2+) transient coordination, we us

110 ated chloride channel TMEM16A, also known as ANO1, in VSMCs, intermediate cells, and pericytes elimin

111 Another network associated with Ano1 includes the SNARE and SM proteins VAMP3, syntaxins

112 The ANO1 inhibitor CaCCinh-A01 decreases proliferation of AN

113 s to elucidate novel biological functions of ANO1 inhibitors.

114 The objective was to identify regions of Ano1 involved in channel gating by Ca2+.

115 ANO1 is a calcium-activated chloride channel that is fre

116 We have found that ANO1 is amplified and highly expressed in breast cancer

117 Whether ANO1 is amplified in breast tumors, the extent to which

118 Understanding the oligomeric nature of Ano1 is an essential step in the development of therapeu

119 For example, Ano1 is highly expressed in multiple tissues including a

120 verexpression, and whether overexpression of ANO1 is important for tumor maintenance have remained un

121 e that inhibition of the channel activity of ANO1 is not sufficient to inhibit ANO1-dependent cell pr

122 Ano1 is overexpressed in cancer.

123 estingly, it appears that in many cell types ANO1 is particularly tightly coupled to the Ca(2+) relea

124 estingly, it appears that in many cell types ANO1 is particularly tightly coupled to the Ca2+ release

125 Ca2+ sensitivity of ANO1 is rather low and at negative membrane potentials t

126 Ca(2+) sensitivity of ANO1 is rather low and at negative membrane potentials t

127 In this study, we show that Ano1 is required to maintain coordinated Ca(2+) transien

128 e approaches, supporting the conclusion that Ano1 is required to maintain coordination/rhythmicity of

129 TMEM16A (ANO1) is a calcium-activated chloride channel (CaCC) exp

130 Anoctamin-1 (Ano1) is a widely expressed protein responsible for endo

131 cium-activated chloride channel anoctamin 1 (ANO1) is located within the 11q13 amplicon, one of the m

132 TMEM16A (also known as anoctamin 1, ANO1) is thought to function as the Ca(2+) activated sec

133 tein 16A (TMEM16A), also called anoctamin 1 (ANO1), is a calcium-activated chloride channel expressed

134 Mice homozygous for Ano1 knock-out exhibit abnormal ICC function and motilit

135 Mechanistically, ANO1 knockdown or pharmacological inhibition of its chlo

136 atiotemporal maps of contractile activity in Ano1 KO and WT tissues.

137 n-rhythmic and uncoordinated was observed in Ano1 KO jejunum.

138 (2+) transients within the ICC-MY network in Ano1 KO mice were uncoordinated, while ICC-MY Ca(2+) tra

139 Voltage-dependent gating of Ano1 measured in the presence of intracellular Ca(2+) wa

140 high-fat diet-fed Ano1(+/-) mice relative to Ano1(+/+) mice fed the same diet.

141 sulin-to-glucose ratios in high-fat diet-fed Ano1(+/-) mice relative to Ano1(+/+) mice fed the same d

142 in metabolism, we carried out experiments in Ano1(+/-) mice.

143 mpetus for gaining a deeper understanding of ANO1 modulation in cells and introduce a new targeting a

144 unctionally characterized approximately 6000 ANO1 mutants and identified novel mutations that affecte

145 The novel ANO1 mutants reported have diverse functional characteri

146 n be defined by the presence of c-Kit, CD34, Ano1, NTPDase2, connexin 43, vimentin, desmin, PDGFbeta

147 Deficiency in Ano1 or Gardos channel did not reduce platelet responses

148 activated Cl(-) channel (CaCC), Anoctamin 1 (Ano1 or TMEM16A), has been implicated in vital physiolog

149 terozygous of homozygous deficiency in Ano6, Ano1, or Ca(2+)-dependent KCa3.1 Gardos channel.

150 t to which gene amplification contributes to ANO1 overexpression, and whether overexpression of ANO1

151 in ICC and are consistent with the idea that ANO1 participates in pacemaker activity.

152 Quantum chemical calculations (CCSD(T)/ANO1) predict an unsymmetrical equilibrium structure for

153 This study identifies the Ano1 promoter and defines a mechanism for regulating its

154 ANO1 promoter methylation was also correlated with patie

155 Hypermethylation of the ANO1 promoter was strongly correlated with but not suffi

156 were used to induce hypermethylation of the ANO1 promoter.

157 ANO1 protein is expressed abundantly and specifically in

158 Washout of CaCCinh-A01 rescued ANO1 protein levels and resumed cell proliferation.

159 We report that CaCCinh-A01 reduces ANO1 protein levels by facilitating endoplasmic reticulu

160 Consistently, CaCCinh-A01 failed to reduce ANO1 protein levels in these cells, whereas ANO1 current

161 -A01 inhibits cell proliferation by reducing ANO1 protein levels.

162 The calcium-activated chloride channel ANO1 regulates multiple physiological processes.

163 rovide a comprehensive footprint of putative Ano1 regulatory networks.

164 nts on T84 cells, which endogenously express Ano1, showed a 2.1 +/- 0.12-fold increase in binding of

165 noprecipitation studies revealed that tagged Ano1 subunits directly associated before they reached th

166 embrane protein 16A (TMEM16A), also known as ANO1, the pore-forming subunit of a Ca(2+) -dependent Cl

167 n the muscle layers, ICC selectively express Ano1, thought to underlie classical Ca(2+)-activated Cl(

168 Although the founding members ANO1 (TMEM16A) and ANO2 (TMEM16B) are Ca(2+)-activated C

169 ntly become possible with the discovery that Ano1 (TMEM16a) is an essential subunit of CaCCs.

170 Ano1 (Tmem16a), a Ca(2+)-activated Cl(-) channel, is an

171 Anoctamin-1 (ANO1, TMEM16A) is a principal CaCC subunit in many cell

172 inal acidification and provide evidence that ANO1/TMEM16A acts to attenuate this pH shift.

173 The identification of ANO1/TMEM16A as the likely calcium-dependent chloride ch

174 asure intraluminal pH and test the idea that ANO1/TMEM16A contributes to luminal pH balance.

175 We conclude that ANO1/TMEM16A is a significant pathway in pancreatic acin

176 ly in ciliogenesis and chloride transport by ANO1/TMEM16A is required for the genesis or maintenance

177 ne conductance regulator (CFTR), anoctamin-1(ANO1/TMEM16A) and the glycine receptor (GlyR), revealed

178 (2+)-activated Cl ((-)) channel anoctamin-1 (ANO1/TMEM16A) is located in the primary cilium and that

179 The calcium-dependent chloride channel DOG1 (ANO1/TMEM16A), which is strongly and specifically expres

180 levels of TRPP1, TRPC1, TRPC3, TRPC6, TRPM4, ANO1/TMEM16A, or voltage-dependent Ca(2+) (CaV1.2) chann

181 We propose an alternative model of Ano1 topology based on mutagenesis, epitope accessibilit

182 The Ca2+ sensitivity of Ano1 was estimated from rates of current activation, and

183 To determine the oligomeric structure of Ano1, we performed chemical cross-linking, non-denaturin

184 SCC datasets with differential expression of ANO1, we showed hypermethylation of positively correlate

185 LS and sufficient to confer this function on ANO1, which normally does not scramble.

186 ntaneous Ca(2+) transients in ICC-MY in both Ano1 WT and knockout (KO) mice.

187 ordinated, while ICC-MY Ca(2+) transients in Ano1 WT mice were rhythmic and coordinated.

188 f Ano1 expression in organotypic cultures of Ano1 WT small intestine.