ライフサイエンスコーパス: adducin

1 of adducin and also inhibited proteolysis of adducin.

2 orylation of the PKC cytoskeletal substrate, adducin.

3 ontrast to the restricted expression of beta-adducin.

4 ization site localized in the neck domain of adducin.

5 -unphosphorylatable S716A/S726A mutant alpha adducin.

6 become artifactually uncapped due to loss of adducin.

7 3-fold and had no effect on interaction with adducin.

8 hange in F-actin binding or association with adducin.

9 d even for an unrelated IDP from human alpha-adducin.

10 n content, decreased band 3, and absent beta-adducin.

11 3 levels and present, although reduced, beta-adducin.

12 use RBCs also contain small amounts of gamma-adducin.

13 n vivo PKC phosphorylation site in mammalian adducins.

14 red blood cells that express alpha and beta adducins.

15 ADD1 (adducin-1) is an actin-binding protein that has been sho

16 to decreased membrane incorporation of alpha-adducin (30% of normal) and unexpectedly promotes a 5-fo

17 beta-Adducin-(335-726) also exhibited a preference for actin

18 The concentration of beta-adducin-(335-726) of 60 nM required for half-maximal bin

19 beta-Adducin-(335-726) promoted recruitment of spectrin to ge

20 natively, that the barbed ends are capped by adducin, a membrane skeleton protein that was shown rece

21 alpha-Adducin, a phosphoprotein that forms a ternary complex w

22 spectrin required for formation of spectrin/adducin/actin complexes in in vitro assays.

23 ptimal participation of spectrin in spectrin/adducin/actin complexes.

24 and of the second repeat in association with adducin/actin, and imply the possibility of an extended

25 egulated downstream targets, including alpha-adducin (ADD1), cyclin D1 (CCND1), and p53.

26 5.1 RNA-binding protein (RNPS1), erythrocyte adducin alpha subunit (ADD1), plexin A3 (PLXNA3 or the S

27 l functions, including altered expression of adducin-alpha, pallidin, stathmin-like-2, and synaptojan

28 ition, we observed that spectrin, actin, and adducin also form a 2D polygonal lattice structure, rese

29 Adducin, an actin-capping protein, colocalized with the

30 patial organizations of spectrin, actin, and adducin, an actin-capping protein, in the dendrites and

31 io and increased phosphorylation (Ser724) of adducin, an F-actin capping protein.

32 aurosporine inhibited PKC phosphorylation of adducin and also inhibited proteolysis of adducin.

33 erable overlap in diffusion coefficients for adducin and ankyrin-tethered populations.

34 activation was dependent on the presence of adducin and its phosphorylation at serine 726.

35 ing was inhibited by phosphorylation of beta-adducin and of a MARCKS-related domain peptide by PKA an

36 A novel difference between adducin and other previously described capping proteins

37 produced from the first eight exons of beta-adducin and part of the neo cassette in spleen but is no

38 logically binds to the cytoskeletal proteins adducin and spectrin, whose mutual interactions are pert

39 f the protein kinase C (PKC) substrate alpha-adducin and the abrogation of DNA damage checkpoint also

40 zation of double knock-out mice lacking beta-adducin and the headpiece domain of dematin.

41 II caused a 60% decrease in endogenous gamma-adducin and was associated with a 2-fold increase in bas

42 diated loss of the host cytoskeletal protein adducin and weakening of the cellular cytoskeleton.

43 ombinant ERK2 phosphorylated alpha- and beta-adducins and dematin at the ERK consensus motif.

44 to the spectrin-actin junctional complex via adducin, and (iii) a freely diffusing population.

45 major peripheral membrane proteins spectrin, adducin, and actin were greatly reduced in FLKO erythroc

46 whereas approximately 33% is immobilized by adducin, and approximately 27% is not attached to any cy

47 that involves interactions between spectrin, adducin, and band 3.

48 Because homologues of dematin, adducin, and glucose transporter-1 exist in many non-ery

49 The hts gene encodes the only Drosophila Adducin, and is a female-sterile mutant that affects bot

50 ization resistant and sensitive to spectrin, adducin, and nucleator deficiency, consistent with micro

51 ructures alternating with those of actin and adducin, and the distance between adjacent actin-adducin

52 ld-type membranes, but levels of actin, TMs, adducins, and other membrane skeleton proteins remain un

53 Spectrin-adducin-ankyrin complexes link membranes to the actin cy

54 We have cloned a cDNA encoding Aplysia adducin (ApADD), the Aplysia homolog of mammalian adduci

55 Dematin and adducin are actin-binding proteins located at the spectr

56 Dematin and adducin are actin-binding proteins of the erythrocyte "j

57 In RBCs, beta- and gamma-adducin are also absent, indicating that alpha-adducin i

58 Adducins are a family of cytoskeletal proteins encoded b

59 Adducins are a family of cytoskeleton proteins encoded b

60 Comparison of the amounts of adducin associated with membranes prepared in the presen

61 PKA, in addition, phosphorylated alpha-adducin at Ser-408, -436, and -481 in the neck domain.

62 RIIA, or by treatment with PMA phosphorylate adducin at Ser726.

63 A rapid phosphorylation of adducin at serine 726 was detected in response to these

64 F-actin with a Kd of 26 microM, and promoted adducin binding to F-actin with half-maximal activation

65 in a 2-fold increased activity in promoting adducin binding with half-maximal activation at 50 nM.

66 t not the extent, of phosphorylation of beta-adducin, but not alpha-adducin, by PKA and that of each

67 osphorylation of beta-adducin, but not alpha-adducin, by PKA and that of each subunit by PKC.

68 Here, we provide evidence Hts/Adducin can serve this function.

69 , corresponding to previously published beta-adducin cDNA sequences beta-1 and beta-2.

70 c activation of the alpha2-Na/K ATPase/alpha-adducin complex as a critical glial cell-intrinsic mecha

71 Adducin contains N-terminal core, neck, and C-terminal t

72 phosphorylation-dependent regulation of Hts/Adducin controls the level, localization, and activity o

73 ents in the membrane skeleton indicates that adducin could be the functional barbed end capper in ery

74 sly described sph alleles reveals band 3 and adducin deficiency as well.

75 ticle tracking in wild-type and ankyrin- and adducin-deficient erythrocytes.

76 d 3 -/- red blood cells contain protein 4.1, adducin, dematin, p55, and glycophorin C.

77 Experiments with recombinant alpha adducin demonstrated that the PKC-phosphorylated form wa

78 In situ hybridization for alpha- and beta-adducin demonstrates that these mRNAs are found througho

79 o mediate the impaired AJ and TJ assembly in adducin-depleted cells.

80 osphorylation of serines 713 and 726 in beta-adducin disrupts cytoskeletal protein complexes and inte

81 ence of magnesium reveals that 60-80% of the adducin dissociates from the membrane during hemolysis a

82 e regions in other proteins (e.g. MacMARCKS, adducin, Drosophila A kinase anchor protein 200, and N-m

83 nslocation of phosphoserine 713 and 726 beta-adducin either to nuclei, where it associates with nucle

84 eover, the cells expressing the mutant alpha adducin exhibited increased levels of cytoplasmic spectr

85 This study presents evidence that adducin exhibits a preference for the fast growing ends

86 Moreover, we characterized PKC delta and p-adducin expression in a pulmonary epithelial cell line (

87 port our hypothesis that a decrease in gamma-adducin expression in cardioregulatory-relevant brain ar

88 nfirmed by demonstrating a decrease in gamma-adducin expression in hypothalamic/brainstem neuronal cu

89 -mediated down-regulation of alpha- or gamma-adducin expression significantly attenuated calcium-depe

90 A similar decrease in gamma-adducin expression was observed in the hypothalamus and

91 The adducin family of proteins interacts with the actin cyto

92 ynaptic plasticity to elucidate the role the adducin family plays in processes underlying learning an

93 nown to markedly reduce the affinity of beta-adducin for spectrin and actin and to uncouple actin/spe

94 by PKA, but not PKC, reduced the affinity of adducin for spectrin-F-actin complexes as well as the ac

95 Chilling releases adducin from the detergent-resistant cytoskeleton.

96 eciprocal relationship between regulation of adducin function by calmodulin binding and phosphorylati

97 Our results suggest that regulation of adducin function by PKC and calpain may play a role in p

98 actin cytoskeleton, suggesting that impaired adducin function may lead to neuromotor impairment and f

99 Adducin functions as a barbed-end actin capping protein

100 and 726 and raise the possibility that beta-adducin functions in support of structure of heterochrom

101 size to the corresponding exons of the alpha-adducin gene (4p16.3), suggesting gene duplication.

102 e intron-exon organization of the human beta-adducin gene (ADD2) has been determined from overlapping

103 ment of the SH rat failed to normalize gamma-adducin gene expression.

104 Adducin has activities in in vitro assays of association

105 A genetic variant in alpha-adducin has been associated with renal sodium reabsorpti

106 data suggest that although the ankyrin- and adducin-immobilized band 3 can be monitored separately,

107 The relative activities of adducin imply that an important role of adducin in cells

108 which was colocalized with the mutant alpha adducin in a punctate pattern.

109 A (p.G367D) mutation in ADD3, encoding gamma adducin in all affected members of the index family.

110 s of adducin imply that an important role of adducin in cells is to form a complex with the fast grow

111 ain, was used to evaluate phosphorylation of adducin in cells.

112 Manipulations of the actin-capping protein adducin in Drosophila and mammalian neurons provide new

113 ium regulation of actin filament assembly by adducin in erythrocytes and at cell-cell contact sites i

114 n ortholog hts confirmed a critical role for adducin in locomotion.

115 phorylation of the actin-stabilizing protein ADDUCIN in MDS samples.

116 ed phosphorylation of the PKCdelta substrate adducin in migrating cells.

117 Knockdown of alpha2-Na/K ATPase or alpha-adducin in mutant SOD1 astrocytes protected motor neuron

118 The concentration of adducin in platelets was estimated at 6 microM, similar

119 revealed the RTPS-serine phosphorylation of adducin in postsynaptic areas in the developing rat hipp

120 F-actin complexes as well as the activity of adducin in promoting binding of spectrin to F-actin.

121 that PTN stimulates the degradation of beta-adducin in PTN-stimulated cells.

122 The lack of beta-adducin in RBCs leads to decreased membrane incorporatio

123 tin polymerization and abolished activity of adducin in recruiting spectrin to ends and sides of acti

124 ransporter-1 as the receptor for dematin and adducin in the human erythrocyte membrane.

125 ults reveal an essential role of dematin and adducin in the maintenance of erythrocyte shape and memb

126 he ubiquitous expression of alpha- and gamma-adducins in contrast to the restricted expression of bet

127 ypertensive rats and (2) analyze the role of adducins in neurotransmission at the cellular level.

128 y, our findings indicate a critical role for adducins in regulating the activity of the actin cytoske

129 These findings suggest novel roles for adducins in stabilization of epithelial junctions and re

130 This study elucidates roles of adducins in the remodeling of epithelial junctions in hu

131 and its substrate, phosphorylated-adducin (p-adducin), in cells of the lung.

132 Rac-1 GTPase and the actin-binding protein, adducin, in human erythroblasts.

133 Platelets express alpha and gamma adducins, in contrast to red blood cells that express al

134 pectedly promotes a 5-fold increase in gamma-adducin incorporation into the RBC membrane skeleton.

135 the level, localization, and activity of Hts/Adducin, influencing actin-based synapse elaboration and

136 KC phosphorylation of native and recombinant adducin inhibited actin capping measured using pyrene-ac

137 ssociated actin filaments that are capped by adducin instead of capZ.

138 The diuretic-adducin interaction was not confounded by traditional ca

139 The point estimates of the diuretic-adducin interaction were similar in separate analyses of

140 modifies in vitro and in vivo activities of adducin involving actin and spectrin, and we demonstrate

141 Adducin is a heteromeric protein with subunits containin

142 Adducin is a membrane skeleton protein originally descri

143 actin and spectrin, and we demonstrate that adducin is a prominent in vivo substrate for PKC or othe

144 Adducin is a protein associated with spectrin and actin

145 Adducin is a protein organizing the cortical actin cytos

146 These data demonstrate that adducin is a significant in vivo substrate for PKC or ot

147 alpha-Adducin is absent in all tissues examined in homozygous

148 Similarly, gamma-adducin is absent in alpha-null platelets.

149 Adducin is an actin-binding protein that has been propos

150 Thus, the RTPS-serine of adducin is an in vivo phosphorylation site for PKC or ot

151 Adducin is associated with regions of cell-cell contact

152 idence that the synaptic localization of Hts/Adducin is controlled via phosphorylation.

153 We show that Drosophila Hts/Adducin is enriched both pre- and postsynaptically at th

154 beta-adducin is expressed at high levels in brain and hematop

155 osphorylation of serines 713 and 726 in beta-adducin is known to markedly reduce the affinity of beta

156 We then demonstrate that presynaptic Hts/Adducin is necessary and sufficient to control two oppos

157 Surprisingly, the head domain of adducin is not required for spectrin-actin interactions,

158 In the red blood cell (RBC), adducin is present primarily as tetramers of alpha- and

159 ducin are also absent, indicating that alpha-adducin is the limiting subunit in tetramer formation at

160 he alternative splice sites for the smallest adducin isoform, beta-3, are alternative donor and accep

161 er analysis of tissue-specific expression of adducin isoforms and in analysis of DNA from patients wi

162 is study we demonstrate a novel function for adducin; it completely blocks elongation and depolymeriz

163 beta-Adducin knock-out mice were examined in physiological an

164 Furthermore, beta-adducin knock-out mice were impaired in performance of f

165 apidly in acute hippocampal slices from beta-adducin knock-out mice, although baseline spine morpholo

166 ly increased in hippocampal slices from beta-adducin knock-out mice.

167 e adducin's role in vivo, we generated alpha-adducin knockout mice.

168 impairs the normal actin-capping function of adducin, leading to both abnormal proliferation and migr

169 Synapse remodeling is sensitive to Hts/Adducin levels, and we provide evidence that the synapti

170 vary, membrane skeletal proteins such as the adducin-like Hts protein(s), spectrin, and ankyrin are f

171 a fusome, containing alpha-spectrin and the adducin-like product of the hu-li tai shao (hts) gene.

172 Alpha-spectrin and the adducin-like protein Hu-li tai shao (Hts) are required t

173 e we propose a new model whereby dematin and adducin link the junctional complex to human erythrocyte

174 We subsequently studied the effects of adducin loss of function in Drosophila.

175 DARPP-32 binds to adducin MARCKS domain and this interaction is modulated

176 Hts/Adducin may define a mechanism to switch between synapse

177 The current results indicate that beta-adducin may play an important role in the cellular mecha

178 Thus, adducins may be involved in changes in cytoskeletal orga

179 nk membranes to the actin cytoskeleton where adducins mediate specrtrin-actin interactions.

180 that PKCalpha-mediated signals, probably via adducin-mediated inhibition of actin-spectrin binding an

181 bed end capping activity requires the intact adducin molecule and is not provided by the NH2-terminal

182 ly at the two weak poly(A) sites of the beta-adducin mRNA.

183 nd actin and to uncouple actin/spectrin/beta-adducin multimeric complexes needed for cytoskeletal sta

184 mplex and its formation of a new bridge with adducin necessitates a significant revision of accepted

185 date adducin's role in vivo, we created beta-adducin null mice by gene targeting, deleting exons 9-13

186 beta-adducin null RBCs are osmotically fragile, spherocytic,

187 alpha-Adducin-null mice display compensated hemolytic anemia w

188 alpha-Adducin-null mice show growth retardation at birth and t

189 ariety of cells, and that phosphorylation of adducin occurs in dendritic spines that are believed to

190 ta, phosphorylating the cytoskeletal protein adducin of both Ser-726 and Thr-445.

191 Actin and phosphorylated adducin of Rac1(-/-);Rac2(-/-) erythrocytes were more ea

192 Platelets contain alpha- and gamma-adducin only.

193 rin, ankyrin, protein 4.2, protein 4.1, beta-adducin, or dematin headpiece exhibited GEs bound to the

194 Loss of function studies of the Drosophila adducin ortholog hts confirmed a critical role for adduc

195 PKC delta and its substrate, phosphorylated-adducin (p-adducin), in cells of the lung.

196 PTN determines the cellular location of beta-adducin phosphorylated in serines 713 and 726 and raise

197 Inhibition of PKC blunts adducin phosphorylation and release from spectrin and ac

198 Adducin phosphorylation at serine 726 was dependent on C

199 additionally evaluated the effect of RhoA on adducin phosphorylation because RhoA activation was show

200 esmosomal adhesion by RhoA- and PKC-mediated adducin phosphorylation in keratinocytes.

201 re to a novel enriched environment increases adducin phosphorylation in WT, but not T75A mutant mice.

202 Adducin phosphorylation is protective, because phosphory

203 gly, however, inhibition of PKCalpha reduced adducin phosphorylation only at Ser-726.

204 echanistically link autoantibody binding and adducin phosphorylation, we evaluated the role of severa

205 These data indicate that adducin plays a role in RBC membrane stability and in ce

206 Gene profiling data coupled with adducin polymorphism studies led us to hypothesize that

207 Adducin promotes association of spectrin with actin and

208 Mechanistically, Drosophila Hts/Adducin protein has actin-capping activity.

209 n (TM) and the other actin-binding proteins, adducin, protein 4.9, tropomodulin, and a small proporti

210 ponse element binding protein (CREB), c-Jun, adducin, protein kinase C, and signal transducer and act

211 Platelet activation also led to adducin proteolysis; inhibition by calpeptin suggests th

212 suggest that the cytoskeleton regulator beta-Adducin provides an activity-dependent switch controllin

213 of cytoskeletal substrate proteins, such as adducin, provides a mechanistic link between increased P

214 Adducin regulates synaptic remodeling, providing a molec

215 al MARCKS-related domains of alpha- and beta-adducin, respectively, were identified as the major phos

216 cin, and the distance between adjacent actin-adducin rings was comparable to the length of a spectrin

217 This study demonstrates adducin's importance to RBC membrane stability in vivo.

218 To elucidate adducin's role in vivo, we created beta-adducin null mic

219 To further define adducin's role in vivo, we generated alpha-adducin knock

220 Phospho-Thr75-DARPP-32 facilitates beta-adducin Ser713 phosphorylation through inhibition of a c

221 We found that adducin silencing induced disruption of the actin cytosk

222 Perfusion of a gamma-adducin-specific antibody caused a 2-fold increase in th

223 e possibility of an extended contact between adducin, spectrin, and actin involving several actin sub

224 embrane skeletal elements including ankyrin, adducin, spectrin, and the junctional complex of the ske

225 e fragmentation, we conclude that the band 3-adducin-spectrin bridge is important to membrane stabili

226 demonstrate the existence of a novel band 3-adducin-spectrin bridge that connects the spectrin/actin

227 However, only the gamma-adducin subunit expression was 40% to 60% lower in the S

228 he present study were to (1) determine which adducin subunit gene demonstrates altered expression in

229 All three adducin subunits (alpha, beta, and gamma) were present i

230 ed domain, present in alpha, beta, and gamma adducin subunits, binds calmodulin and contains the majo

231 phasing and belongs to the class II aldolase/adducin superfamily.

232 In mice, the beta-Adducin switch is required for the improvement of learni

233 We conclude that adducin targets actin filament ends to spectrin to compl

234 ctin 1-Smooth muscle gamma actin-D6Mm4e-beta-adducin-telomere.

235 l that mobilities of individual ankyrin- and adducin-tethered band 3 molecules are heterogeneous, var

236 ls expressed the alpha and gamma isoforms of adducin that positively regulated each others protein le

237 in (ApADD), the Aplysia homolog of mammalian adducins that are regulatory components of the membrane

238 y virtue of its interaction with ankyrin and adducin, the anion transporter, band 3 (AE1), contribute

239 otein kinase (PK) C substrate domain of beta-adducin through activation of either PKC alpha or beta.

240 to regulate tyrosine phosphorylation of beta-adducin through the PTN/receptor protein tyrosine phosph

241 nsmembrane protein that binds to dematin and adducin, thus providing a rationale for the attachment o

242 ritical region, impairs the ability of gamma adducin to associate with the alpha subunit.

243 he half-maximal concentration for binding of adducin to gelsolin-sensitive sites at filament ends was

244 eton) revealed a shift of PKC-phosphorylated adducin to the cytosol during platelet activation.

245 Among the 385 carriers of the adducin variant allele, diuretic therapy was associated

246 uretic use would be lower in carriers of the adducin variant than in carriers of the adducin wild-typ

247 The OR in carriers of the adducin variant was less than half of the OR in carriers

248 The adducin variant was present in more than one third of th

249 In carriers of the adducin variant, diuretic therapy was associated with a

250 A hypertension-linked decrease of gamma-adducin was confirmed by demonstrating a decrease in gam

251 tein complex of alpha2-Na/K ATPase and alpha-adducin was enriched in astrocytes expressing mutant sup

252 in kinase C substrate-related domain of beta-adducin was identified as the dominant Ca2+-dependent ca

253 The mutant alpha adducin was no longer concentrated at the cell membrane

254 Both PKC delta and p-adducin were almost exclusively expressed in bronchiolar

255 Notably, alpha2-Na/K ATPase and alpha-adducin were upregulated in spinal cord of sporadic and

256 bol 12-myristate 13-acetate, alpha and gamma adducins were phosphorylated by protein kinase C (PKC) a

257 protein in striatal neurons, interacts with adducins, which are cytoskeletal proteins that cap actin

258 with the cytoskeletal proteins spectrin and adducin whose altered disposition in IP6K3 knock-out mic

259 Among the 653 carriers of the adducin wild-type genotype, diuretic therapy was not ass

260 the adducin variant than in carriers of the adducin wild-type genotype.

261 All interactions of adducin with actin require the myristoylated alanine-ric

262 The association of stoichiometric amounts of adducin with the short erythrocyte actin filaments in th