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 with levels of a marker of dendritic spines, spinophilin.

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

11 atase substrates and the PP1-binding protein spinophilin.

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

13 alized Rac activation dependent on Tiam1 and spinophilin.

14 utations at the PKA phosphorylation sites of spinophilin.

15 ock-transfected cells or in cells expressing spinophilin.

16 d by protein phosphatase 1 and its regulator spinophilin.

17 4-3-3 epsilon are blocked in the presence of spinophilin.

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

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

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

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

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

23 Spinophilin, a protein that interacts with actin and pro

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

25 Spinophilin, a recently characterized F-actin and protei

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

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

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

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

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

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

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

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

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

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

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

37 Spinophilin and neurabin contain a single PDZ domain, a

38 Recombinant spinophilin and neurabin interacted with endogenous PP1

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

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

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

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

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

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

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

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

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

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

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

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

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

52 potentiation and levels of synaptic markers spinophilin and VGLUT1.

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

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

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

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

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

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

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

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

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

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

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

64 Neurabin and spinophilin are homologous protein phosphatase 1 and act

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

66 Neurabin and spinophilin are neuronal scaffolding proteins that play

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

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

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

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

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

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

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

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

75 In particular, spinophilin binding promotes the plasma membrane localiz

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

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

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

79 Decreased spinophilin but unchanged MAP2 expression provides molec

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

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

82 Phosphorylation of spinophilin by PKA modulated the association between spi

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

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

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

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

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

88 lum, irrespective of regional differences in spinophilin concentration.

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

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

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

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

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

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

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

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

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

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

99 Mice lacking spinophilin expression display dramatically enhanced and

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

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

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

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

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

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

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

107 Spinophilin has the properties expected of a scaffolding

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

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

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

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

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

113 Spinophilin immunoreactivity was present throughout the

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

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

116 Cdk5 and ERK2 both phosphorylated spinophilin in intact cells.

117 Conversely, deleting spinophilin in mice inhibits platelet activation.

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

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

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

121 2short third cytoplasmic loops interact with spinophilin in vitro and in yeast two-hybrid assays.

122 Spinophilin, in turn, regulates interaction of G protein

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

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

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

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

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

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

129 Spinophilin is a protein that binds to protein phosphata

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

131 Spinophilin is an actin binding protein that positions p

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

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

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

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

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

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

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

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

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

141 In addition, spinophilin is present postsynaptic to asymmetrical cont

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

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

144 Spinophilin knock-out results in enhanced mGluR5 endocyt

145 Spinophilin knockout mice were more sensitive than wild-

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

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

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

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

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

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

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

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

154 Thus, spinophilin may play analogous roles in information tran

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

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

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

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

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

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

161 cells lacking spinophilin or expressing the spinophilin mutant Sp177D.

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

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

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

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

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

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

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

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

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

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

172 Immunoprecipitation of spinophilin or neurabin from crude brain extracts select

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

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

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

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

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

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

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

180 Spinophilin plays critical roles in regulating trafficki

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

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

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

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

185 Therefore, modulation of spinophilin-receptor interaction through phosphorylation

186 Spinophilin recruits Asef2 to spines, and knockdown of s

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

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

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

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

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

192 Spinophilin residues 427-470, or homologous neurabin res

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

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

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

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

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

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

199 Spinophilin (SPL), a multidomain scaffolding protein kno

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

218 Phosphorylation of spinophilin was stimulated by treatment of neostriatal n

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

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

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

222 2 interacts with the F-actin-binding protein spinophilin, which localizes to spines, we investigated

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

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

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

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

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