ライフサイエンスコーパス: spinophilin

1 e with VGKCs, but partially co-localize with spinophilin.

2 (Ser-17), within the actin-binding domain of spinophilin.

3 where it interacted with either neurabin or spinophilin.

4 protein phosphatase-1 to its binding protein spinophilin.

5 e located within the actin-binding domain of spinophilin.

6 alpha(2)AR subtypes might also interact with spinophilin.

7 domain is located within residues 417-494 of spinophilin.

8 endritic spines and has therefore been named spinophilin.

9 e fluorescence intensities of phalloidin and spinophilin.

10 with levels of a marker of dendritic spines, spinophilin.

11 ceptor substrate protein 53 kDa (IRSp53) and spinophilin.

12 atase substrates and the PP1-binding protein spinophilin.

13 l adhesion were dependent on IRSp53, but not spinophilin.

14 alized Rac activation dependent on Tiam1 and spinophilin.

15 utations at the PKA phosphorylation sites of spinophilin.

16 ock-transfected cells or in cells expressing spinophilin.

17 d by protein phosphatase 1 and its regulator spinophilin.

18 4-3-3 epsilon are blocked in the presence of spinophilin.

19 lpha2-ARs is modified by RGS4 independent of spinophilin.

20 r its previously described interactions with spinophilin, 14-3-3zeta, and arrestin 3, suggesting that

21 a 2B, and alpha 2C-AR subtypes interact with spinophilin, a multidomain protein that, like the three

22 esent study, the interaction between PP1 and spinophilin, a neuronal protein that targets PP1 to dend

23 The other involves binding of PP-1 to spinophilin, a protein that colocalizes PP-1 with AMPA r

24 Spinophilin, a protein that interacts with actin and pro

25 We find that Spinophilin, a Protein-phosphatase 1 (PP1) targeting pro

26 Spinophilin, a recently characterized F-actin and protei

27 icity in a different way by interaction with spinophilin, a scaffold that binds to p70 S6 kinase, ano

28 One such protein is spinophilin, a scaffolding protein of neuronal dendritic

29 Immunolocalization of spinophilin, a spine-associated protein, was used for qu

30 other proteins besides microtubules, such as spinophilin (abbreviated spn; gene name Ppp1r9b protein

31 spinophilin reduced the stoichiometry of the spinophilin-actin interaction.

32 n of spinophilin, is sufficient to block the spinophilin-alpha(2A)AR interaction in intact cells.

33 phosphorylation of spinophilin modulates the spinophilin-alpha(2A)AR interaction to regulate alpha(2A

34 These interactions could be refined to spinophilin amino acid residues 169-255, in a region bet

35 p binding to glutathione S-transferase (GST)-spinophilin amino acids 151-444 revealed a relative affi

36 and upregulates the dendritic spine protein spinophilin, an effect attenuated by antagonism of the A

37 The reciprocal interactions of GPCRs with spinophilin and arrestin represent a regulatory mechanis

38 lloidin (for F-actin) and immunolabeling for spinophilin and imaged by confocal microscopy.

39 Spinophilin and neurabin contain a single PDZ domain, a

40 Recombinant spinophilin and neurabin interacted with endogenous PP1

41 ic proteins directly and differentially bind spinophilin and neurabin PDZ domains.

42 ed that PP1gamma1 selectively interacts with spinophilin and neurabin, F-actin-targeting proteins, wh

43 e synapse-localized F-actin-binding proteins spinophilin and neurabin, respectively.

44 om brain extracts efficiently coprecipitated spinophilin and neurabin, whereas PP1beta immunoprecipit

45 leukemia-associated RhoGEF), RGS3 and RGS12, spinophilin and neurabin-1, SRC homology 3 domain and mu

46 ers of this family are the neuronal proteins spinophilin and neurabin.

47 characterization of the interactions between spinophilin and PP1 has facilitated the design of peptid

48 of interaction with the targeting subunits, spinophilin and PP1 nuclear targeting subunit (PNUTS).

49 s of the D2 dopamine receptors interact with spinophilin and that spinophilin is enriched beneath the

50 lin by PKA modulated the association between spinophilin and the actin cytoskeleton.

51 hes the agonist-enhanced interaction between spinophilin and the alpha(2A)AR, and this event can be b

52 A direct interaction between spinophilin and the D2 receptor was confirmed in vitro u

53 ochemistry using antibodies directed against spinophilin and the HA tag.

54 potentiation and levels of synaptic markers spinophilin and VGLUT1.

55 Thus, PP1(A) holoenzymes containing spinophilin and/or neurabin target specific neuronal PP1

56 eactivity of postsynaptic markers (PSD95 and spinophilin) and a presynaptic marker (syntaxin) were en

57 a(2A)-AR increases receptor association with spinophilin, and arrestin 3 appears to compete for this

58 trols, we compared dysbindin, synaptophysin, spinophilin, and cyclophilin mRNA levels in the dorsolat

59 al prefrontal cortex, whereas synaptophysin, spinophilin, and cyclophilin mRNA levels were unchanged.

60 apped other cytoskeletal proteins, including spinophilin, and led to increased autophagy.

61 PP1 regulatory/targeting proteins DARPP-32, spinophilin, and neurabin were also unchanged.

62 We report that the multidomain protein, spinophilin, antagonizes these multiple arrestin functio

63 Furthermore, expression of spinophilin appeared to slow, whereas overexpression of

64 In conclusion, spinophilin appears to be required for the regulation of

65 receptor-interacting proteins filamin-A and spinophilin are affected in the dorsolateral prefrontal

66 Neurabin and spinophilin are homologous protein phosphatase 1 and act

67 uggests that the PDZ domains of neurabin and spinophilin are important for targeting PP1 to C-termina

68 Neurabin and spinophilin are neuronal scaffolding proteins that play

69 ptides suggested that distinct subdomains of spinophilin are responsible for binding and modulating P

70 sequential or competitive interactions among spinophilin, arrestin, and/or 14-3-3zeta play a role in

71 tify the multifunctional scaffolding protein spinophilin as a novel Group I mGluR-interacting protein

72 These results identify spinophilin as a novel striatal signaling hub molecule i

73 We previously identified spinophilin as a regulator of alpha(2) adrenergic recept

74 n co-localization of receptor and endogenous spinophilin as determined by immunocytochemistry using a

75 These results collectively point to spinophilin-Asef2-Rac signaling as a novel mechanism for

76 receptors and protein phosphatase-1 may bind spinophilin at the same time.

77 r agonist or with forskolin, consistent with spinophilin being a substrate for PKA in intact cells.

78 In particular, spinophilin binding promotes the plasma membrane localiz

79 In contrast, spinophilin binding suppresses the ability of Tiam to ac

80 r glial fibrillary acidic protein (GFAP) and spinophilin but a 10-fold increased amyloid-beta42.

81 he 3i loop are critical for interaction with spinophilin but not for interaction with 14-3-3zeta or a

82 Decreased spinophilin but unchanged MAP2 expression provides molec

83 he alpha(2A)AR in cells expressing wild type spinophilin, but not in cells lacking spinophilin or exp

84 ing neurons, likely through interaction with spinophilin, but not through alpha-actinin-4 or Arp3.

85 Phosphorylation of spinophilin by PKA modulated the association between spi

86 our studies suggest that phosphorylation of spinophilin by PKA modulates the anchoring of the spinop

87 In cells expressing mutant spinophilin carrying the S177D mutation, agonist-induced

88 alpha(2A) adrenergic receptor (alpha(2A)AR)-spinophilin-cofilin axis in the hippocampus that is crit

89 st-regulated fashion, because alpha2A AR and spinophilin coimmunoprecipitation from cells is enhanced

90 activation in cells, suggesting that a Tiam1/spinophilin complex contributes to p70 S6 kinase regulat

91 ed Rac activation associated with IRSp53 and spinophilin complexes in individual fibroblasts to test

92 lum, irrespective of regional differences in spinophilin concentration.

93 cids 151-444 revealed a relative affinity of spinophilin congruent with arrestin > 14-3-3zeta for the

94 electivity determinant (N(464)EDYDRR(470) in spinophilin: conserved as residues 473-479 in neurabin)

95 de evidence that alpha 2-AR interaction with spinophilin contributes to cell surface stabilization of

96 tent with the interpretation that endogenous spinophilin contributes to the stabilization of alpha 2B

97 In spinophilin-deficient cells, Tiam1 co-localized with IRS

98 ent with altered glutamatergic transmission, spinophilin-deficient mice showed reduced long-term depr

99 on and increased cell migration in a Rac and spinophilin-dependent fashion.

100 Spinophilin-dependent regulation of cofilin is required

101 in 2 and 3, GRK 2 and 3, 14-3-3 epsilon, and spinophilin directly associate with the Na(+),K(+)-ATPas

102 PKA activation results in phosphorylation of spinophilin, disrupting its interaction with alpha2AARs

103 vation because DCs derived from mice lacking spinophilin exhibit defects in antigen presentation both

104 Mice lacking spinophilin expression display dramatically enhanced and

105 These findings suggest that eliminating spinophilin expression in native tissues leads to an enh

106 In addition, the loss of spinophilin expression results in impaired mGluR5-stimul

107 Spinophilin fluorescence was lower across all spine size

108 oprecipitation of neurabin I and neurabin II/spinophilin from rat brain extracts sedimented PP1gamma1

109 These studies support the notion that spinophilin functions in vivo as a neuronal PP1 targetin

110 es interacted with glutathione S-transferase-spinophilin fusion proteins.

111 lytic efficiency of the PP1-Neurabin and PP1-Spinophilin fusions is primarily determined by substrate

112 In addition, deletion of the spinophilin gene caused a marked increase in spine densi

113 With the help of a spinophilin-GFP fusion protein, Bloom et al. have captur

114 Spinophilin has the properties expected of a scaffolding

115 ion of alpha2AARs by the scaffolding protein spinophilin have illuminated a potential novel mechanism

116 n recruits Asef2 to spines, and knockdown of spinophilin hinders spine and synapse formation in Asef2

117 K293 cells expressing GFP-tagged variants of spinophilin, imaging studies demonstrated that introduct

118 r quantitative stereologic analyses of total spinophilin-immunoreactive spine numbers in CA1 stratum

119 e estrogen-treated groups had an increase in spinophilin-immunoreactive spines (37% in young, P <.005

120 Spinophilin immunoreactivity was present throughout the

121 immunoblotting were utilized to identify how spinophilin impacts mGluR5 phosphorylation and protein i

122 lizes to spines, we investigated the role of spinophilin in Asef2-promoted spine formation.

123 Furthermore, COPS5 overexpression reduced spinophilin in both the cortex (19%, p < 0.05) and the h

124 nce of a novel motor repertoire, but loss of spinophilin in either MSN subtype abrogated striatal pla

125 Cdk5 and ERK2 both phosphorylated spinophilin in intact cells.

126 roles of the striatal signaling hub protein spinophilin in mediating repetitive motor dysfunction as

127 Conversely, deleting spinophilin in mice inhibits platelet activation.

128 To assess the generalized role of spinophilin in regulating alpha(2)AR functions in vivo,

129 p53-deficient cells, Tiam1 co-localized with spinophilin in response to forskolin or epinephrine.

130 ncreases the association of PP1gamma(1) with spinophilin in striatal extracts.

131 2short third cytoplasmic loops interact with spinophilin in vitro and in yeast two-hybrid assays.

132 Spinophilin, in turn, regulates interaction of G protein

133 s, GPCR kinases (GRKs), 14-3-3 proteins, and spinophilin interact with GPCRs and modulate the duratio

134 nsible for ADCME, as the loss of alpha2B -AR/spinophilin interaction causes a gain of function effect

135 how that alpha2AR agonist-mediated alpha2AAR/spinophilin interaction is blocked by betaAR co-activati

136 the protein phosphatase 1 regulatory subunit spinophilin interacts with and regulates dephosphorylati

137 is of the modulatory subdomain revealed that spinophilin interacts with PP1 via a mechanism unlike th

138 We demonstrate that spinophilin interacts with the C-terminal tail and secon

139 Spinophilin is a protein phosphatase 1 (PP1)- and actin-

140 Spinophilin is a protein that binds to protein phosphata

141 s, consistent with our previous finding that spinophilin is a substrate for phosphorylation by PKA th

142 Spinophilin is an actin binding protein that positions p

143 receptors interact with spinophilin and that spinophilin is enriched beneath the basolateral surface

144 Here, we show that spinophilin is enriched in the great majority of dendrit

145 strongly support that PKA phosphorylation of spinophilin is functionally relevant in regulating alpha

146 We hypothesize that spinophilin is important for establishing a signaling co

147 In inactive, immature DCs, spinophilin is located throughout the cytoplasm but redi

148 w that, in hippocampus and ventral pallidum, spinophilin is occasionally present in dendritic shafts

149 We report that spinophilin is phosphorylated in vitro by protein kinase

150 In DCs interacting with T cells, spinophilin is polarized dynamically to contact sites in

151 Previous studies suggest that spinophilin is present in most spines, but the concentra

152 In addition, spinophilin is present postsynaptic to asymmetrical cont

153 ted within the alpha(2A)AR binding region of spinophilin, is sufficient to block the spinophilin-alph

154 ibroblasts derived from wild type (Sp+/+) or spinophilin knock-out (Sp-/-) mice.

155 Spinophilin knock-out results in enhanced mGluR5 endocyt

156 Spinophilin knockout mice were more sensitive than wild-

157 Here, through the use of spinophilin knockout mice, we provide evidence that spin

158 -D-aspartate (NMDA) receptors was reduced in spinophilin knockout mice.

159 S4 on alpha2-AR signaling was not altered in spinophilin-knockout mice.

160 postsynaptic density, had a lower density of spinophilin label.

161 mal levels of calcyon, whereas filamin-A and spinophilin levels were unaltered.

162 on with arrestins, GRKs, 14-3-3 epsilon, and spinophilin may be important modulators of Na(+),K(+)-AT

163 These findings suggest that spinophilin may contribute not only to alpha2 AR localiz

164 Thus, the functional role of spinophilin may not be exclusively restricted to excitat

165 Thus, spinophilin may play analogous roles in information tran

166 eptor interaction through phosphorylation of spinophilin may represent a novel mechanism whereby PKA

167 ssion but also suggests the possibility that spinophilin may target protein phosphatase-1 to other si

168 -d-aspartate receptor (NMDA) activity blocks spinophilin-mediated localization of Asef2 to spines.

169 Biochemically, we determined that the spinophilin-mGluR5 interaction correlates with grooming

170 ilin knockout mice, we provide evidence that spinophilin modulates both glutamatergic synaptic transm

171 at protein kinase A (PKA) phosphorylation of spinophilin modulates the spinophilin-alpha(2A)AR intera

172 on were measured using our novel conditional spinophilin mouse model in which spinophilin was knocked

173 ients with schizophrenia had lower levels of spinophilin mRNA in CA4 (hilus), CA3, the subiculum, and

174 cells lacking spinophilin or expressing the spinophilin mutant Sp177D.

175 the F-actin-binding proteins neurabin I and spinophilin (neurabin II) also bind PP1, their role in P

176 oprecipitation of the phosphorylated DCX and spinophilin/neurabin II from DCX-synthesizing glioma cel

177 rinsic affinity for agonist in the brains of spinophilin-null mice compared with wild-type control mi

178 Thus, brain preparations from spinophilin-null mice demonstrate enhanced guanine nucle

179 a(2A)AR to cognate G proteins is enhanced in spinophilin-null mice.

180 -quinoxalinamine (UK14,304) and clonidine in spinophilin-null mice.

181 ion is blocked by PKA inhibition and lost in spinophilin-null neurons, consistent with our previous f

182 tion alone drives accelerated endocytosis in spinophilin-null neurons.

183 ent study examined the impact of eliminating spinophilin on alpha(2)AR-evoked cardiovascular and hypn

184 Loss of spinophilin only in indirect-pathway MSNs decreased perf

185 d type spinophilin, but not in cells lacking spinophilin or expressing the spinophilin mutant Sp177D.

186 Immunoprecipitation of spinophilin or neurabin from crude brain extracts select

187 also allowed us to classify the neurabin and spinophilin PDZ domains as the first identified neuronal

188 port the structures of both the neurabin and spinophilin PDZ domains determined using biomolecular NM

189 of the binding and inhibitory properties of spinophilin peptides suggested that distinct subdomains

190 data also suggest that the concentration of spinophilin per spine is variable and is likely regulate

191 e by increasing PP1gamma(1) interaction with spinophilin, perhaps contributing to hyperphosphorylatio

192 These results support a role for spinophilin phosphorylation by ERK2 in the regulation of

193 al regulators as substrates for the Neurabin/Spinophilin PIPs, implicated in neuronal plasticity, poi

194 Our results indicate that spinophilin plays an important role in regulating the ac

195 Spinophilin plays critical roles in regulating trafficki

196 ensity and postsynaptic density (PSD)-95 and spinophilin-positive clusters in the cortex of HD mice.

197 philin by PKA modulates the anchoring of the spinophilin-PP1 complex within dendritic spines, thereby

198 of peptide antagonists capable of disrupting spinophilin-PP1 interactions.

199 ization correlate with a twofold increase in spinophilin protein and the density of dendritic spines

200 Therefore, modulation of spinophilin-receptor interaction through phosphorylation

201 Spinophilin recruits Asef2 to spines, and knockdown of s

202 ay analysis revealed that phosphorylation of spinophilin reduced the stoichiometry of the spinophilin

203 ociation with receptor-Gbetagamma complexes, spinophilin reduces arrestin-stabilized receptor phospho

204 anonical betaAR-mediated signaling modulates spinophilin-regulated alpha2AAR endocytosis through PKA.

205 The distribution of spinophilin reported in this study supports its role in

206 We propose that spinophilin represents a novel targeting subunit for PP1

207 Spinophilin residues 427-470, or homologous neurabin res

208 The portion of spinophilin responsible for interacting with the D2 thir

209 o acid residues 169-255, in a region between spinophilin's F-actin binding and phosphatase 1 regulato

210 To better understand spinophilin's role in targeting protein phosphatase-1 wi

211 Thus, interaction between Lfc and neurabin/spinophilin selectively regulates Rho-dependent organiza

212 We show here that spinophilin selectively targets PP1gamma1, but not PP1be

213 ates with grooming behavior and that loss of spinophilin shifts mGluR5 interactions from lipid raft-a

214 levels of synaptophysin (SYP) (p < 0.05) and spinophilin (SPH) (p < 0.05) in the olfactory cortex, po

215 Spinophilin (SPL) and neurabin (NRB) are structurally si

216 Spinophilin (SPL), a multidomain scaffolding protein kno

217 vel complex comprising the scaffold protein, spinophilin (SPL), and the tyrosine phosphatase, SHP-1,

218 n platelets is formed by a scaffold protein, spinophilin (SPL), the tyrosine phosphatase, Src homolog

219 m between two conserved regulatory proteins, Spinophilin (Spn) and Syd-1, controls presynaptic long-t

220 eurexin-binding scaffold proteins, Syd-1 and Spinophilin (Spn), spatio-temporally coordinated pre-pos

221 Apical delivery of a spinophilin subdomain containing the alpha 2-AR-interact

222 Finally, a mutant spinophilin that cannot bind to Tiam1 suppresses serum-i

223 us far, it is still unknown how neurabin and spinophilin themselves are targeted to these membrane re

224 ionic acid-type glutamate receptor, Ser94 of spinophilin, Thr34 of the dopamine- and cAMP-regulated p

225 he required targeting of PP1 by neurabin and spinophilin to achieve substrate specificity at the syna

226 the conserved motif abolished the ability of spinophilin to bind PP1, as observed by coprecipitation,

227 by Cdk5, was able to modulate the ability of spinophilin to bind to and bundle actin filaments.

228 In contrast, the ability of spinophilin to bind to PP1 remained unchanged.

229 y or in combination, impaired the ability of spinophilin to coprecipitate PP1.

230 campal neurons responded with an increase in spinophilin to estradiol but not PGE2.

231 with the dendritic spine scaffolding protein spinophilin to induce cofilin activation at the synapse.

232 compete for the agonist-enriched binding of spinophilin to the mutant alpha(2A)-AR.

233 ing the binding with the scaffolding protein spinophilin upon neurotransmitter activation.

234 ent in most spines, but the concentration of spinophilin varies from brain region to region in a mann

235 ink alpha 2-ARs to proteins interacting with spinophilin via other domains.

236 subcellular fractionation, unphosphorylated spinophilin was enriched in the postsynaptic density, wh

237 ic density, whereas a pool of phosphorylated spinophilin was found in the cytosol.

238 Consistent with previous reports, spinophilin was found predominantly in dendritic spines,

239 conditional spinophilin mouse model in which spinophilin was knocked out from striatal direct-pathway

240 Phosphorylation of spinophilin was stimulated by treatment of neostriatal n

241 ic localization of one of these transcripts, spinophilin, was found to be dependent on both ZBP1 and

242 hat are recruited to the receptor complex by spinophilin, whereas the effect of alpha2-ARs is modifie

243 R signaling were lost in mutant mice lacking spinophilin, which binds several RGS members and G prote

244 2 interacts with the F-actin-binding protein spinophilin, which localizes to spines, we investigated

245 expression of two important dendritic genes: spinophilin, which serves as a marker of dendritic spine

246 Furthermore, we show that interaction of spinophilin with Group I mGluRs attenuates receptor endo

247 Coexpression of neurabin or spinophilin with Lfc resulted in their clustering togeth

248 ct that is dependent upon the interaction of spinophilin with the C-terminal PDZ binding motif encode

249 hod, we further examined the distribution of spinophilin within dendritic spines.