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 order of AD via phosphorylation of Ser726 on adducin 1 (Add1).

16 or APC signaling, a function for afadin and adducin-1 actin binding proteins in thrombin-induced end

17 However, loss of adducin-1 blocked APC-induced Akt signaling.

18 ombin-promoted barrier permeability, whereas adducin-1 depletion completely ablated thrombin-induced

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

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

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

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

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

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

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

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

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

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

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

30 ous studies have implicated a role for gamma-adducin (ADD3), a cytoskeletal protein encoded by Add3.

31 5.1 RNA-binding protein (RNPS1), erythrocyte adducin alpha subunit (ADD1), plexin A3 (PLXNA3 or the S

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

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

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

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

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

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

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

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

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

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

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

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

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

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

46 tructure in which actin filaments, capped by adducin and tropomodulin, form ring-shaped structures co

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

64 Adducins are a family of cytoskeletal proteins encoded b

65 Adducins are a family of cytoskeleton proteins encoded b

66 o minor isoforms of the actin regulator hts (adducin), as well as mildly reducing expression of CalpA

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

98 The adducin family of proteins interacts with the actin cyto

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

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

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

102 Chilling releases adducin from the detergent-resistant cytoskeleton.

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

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

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

106 Adducin functions as a barbed-end actin capping protein

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

108 Additionally, adducin-gamma localizes to tight junctions in response t

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

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

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

112 Adducin has activities in in vitro assays of association

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

114 x-IV) and the membrane cytoskeletal effector Adducin/Hu-li tai shao (Hts) as proteins whose synaptic

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

150 Adducin is a heteromeric protein with subunits containin

151 Adducin is a membrane skeleton protein originally descri

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

153 Adducin is a protein associated with spectrin and actin

154 Adducin is a protein organizing the cortical actin cytos

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

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

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

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

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

160 Adducin is associated with regions of cell-cell contact

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

201 Platelets contain alpha- and gamma-adducin only.

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

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

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

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

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

207 bilization through protein kinase C-mediated adducin phosphorylation and to spectrin degradation by c

208 We identified beta-adducin phosphorylation as a Cdk5 downstream mechanism p

209 Adducin phosphorylation at serine 726 was dependent on C

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

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

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

213 Adducin phosphorylation is protective, because phosphory

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

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

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

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

218 Adducin promotes association of spectrin with actin and

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

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

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

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

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

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

225 Adducin regulates synaptic remodeling, providing a molec

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

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

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

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

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

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

232 haviors in HD mice by altering DARPP-32/beta-adducin signaling and disrupting the dendritic spine cyt

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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