ライフサイエンスコーパス: NCS-1

1 NCS-1 and PI4Kbeta coimmunoprecipitate, opening up the p

2 NCS-1 and TRPC5 are in the same protein complex in rat b

3 NCS-1 binds directly to PICK1 via its BAR domain in a Ca

4 NCS-1 is a multispecific protein interacting with a numb

5 NCS-1 was shown to modulate the effects of expression of

6 NCS-1-D2 receptor interaction may serve to couple dopami

7 that the neuronal calcium sensor protein-1 (NCS-1), another member of the recoverin-neuronal calcium

8 n, which degrades neuronal calcium sensor 1 (NCS-1) and subsequent loss of intracellular calcium sign

9 the Ca(2+) sensor neuronal calcium sensor 1 (NCS-1) and the guanine exchange factor protein Ric8a cor

10 Neuron specific calcium sensor 1 (NCS-1) is widely expressed in the developing and adult n

11 ific reduction in neuronal calcium sensor 1 (NCS-1) protein levels, a known modulator of InsP(3) rece

12 l binding protein, neuronal Ca(2+) sensor 1 (NCS-1), a Ca(2+) binding protein that interacts with the

13 tween paclitaxel, neuronal calcium sensor 1 (NCS-1), and the inositol 1,4,5-trisphosphate receptor (I

14 ess I(Ca), unless neuronal calcium sensor-1 (NCS-1) activity was blocked by a dominant-negative NCS-1

15 heral neuropathy, neuronal calcium sensor-1 (NCS-1) and calpain.

16 teraction between neuronal calcium sensor-1 (NCS-1) and the GTPase ARF1.

17 ts mammalian homolog neuronal Ca2+ sensor-1 (NCS-1) belong to a family of Ca2+ sensors with EF hands

18 we show that the neuronal calcium sensor-1 (NCS-1) can mediate desensitization of D2 dopamine recept

19 m binding protein neuronal calcium sensor-1 (NCS-1) can switch paired-pulse depression to facilitatio

20 eins (KChIPs) and neuronal calcium sensor-1 (NCS-1) have been shown to interact with Kv4 channel alph

21 Neuronal calcium sensor-1 (NCS-1) is a small calcium binding protein that plays a k

22 Neuronal calcium sensor-1 (NCS-1) is the primordial member of a family of proteins

23 Neuronal calcium sensor-1 (NCS-1) is the primordial member of the neuronal calcium

24 Neuronal calcium sensor-1 (NCS-1) mediates changes in cellular function by regulati

25 ism involving the neuronal calcium sensor-1 (NCS-1) protein.

26 Neuronal calcium sensor-1 (NCS-1), a Ca(2+)-binding protein, plays an important rol

27 tudy, addition of neuronal calcium sensor-1 (NCS-1), a high-affinity, low-capacity, calcium-binding p

28 with that of the neuronal calcium sensor-1 (NCS-1), a neuron-specific calcium-binding and D2-interac

29 -binding protein, neuronal calcium sensor-1 (NCS-1), can physically associate with the type III PI4Kb

30 in, also known as neuronal calcium sensor-1 (NCS-1), is an N-myristoylated Ca2+-binding protein that

31 mination of the crystal structures of Ca(2+)/NCS-1 alone and in complex with peptides derived from D2

32 ind within the hydrophobic crevice on Ca(2+)/NCS-1, but only one copy of the GRK1 peptide binds.

33 In the Ca(2+)/NCS-1.D2R peptide complex, the C-terminal region adopts

34 hat this adaptive signalling network (Cav1.3/NCS-1/D2/GIRK2) is also active in human SN DA neurons, a

35 in the same protein complex in rat brain and NCS-1 directly binds to the TRPC5 C-terminus.

36 ly block the interaction between the D2R and NCS-1.

37 errogate the interaction between the D2R and NCS-1.

38 Furthermore, in vitro, Frq1 and NCS-1 (either N-myristoylated or unmyristoylated) compet

39 is with chimeric proteins between KChIP2 and NCS-1 reveals that the three regions of KChIP2 (the link

40 ce in these three regions between KChIPs and NCS-1 determines the specificity and affinity for intera

41 When expressed in COS-7 cells, PI4Kbeta and NCS-1 formed a complex that could be immunoprecipitated

42 Transfection of PI4Kbeta and NCS-1 had no effect on basal PIP synthesis in permeabili

43 osphoinositide-mediated Ca(2+) signaling and NCS-1 protein levels.

44 Inhibitory mutants of TRPC5 and NCS-1 enhance neurite outgrowth similarly.

45 and PI 4-kinase activity was present in anti-NCS-1 immunoprecipitates.

46 suggest protein-protein interaction between NCS-1 and TRPC5, and involvement of this protein complex

47 In the developing olfactory bulb, NCS-1 was expressed in the processes of mitral/tufted an

48 and D2-autoreceptor activity, controlled by NCS-1, and indicate that this adaptive signalling networ

49 the different molecular states populated by NCS-1 was monitored in real time through constant-force

50 Like calmodulin, NCS-1 is a member of a family of calcium binding protein

51 Expressed NCS-1-YFP showed co-localization with endogenous PI4Kbet

52 First, NCS-1 levels and intracellular calcium signaling were fo

53 as a physiological cofactor with calcium for NCS-1-D2R binding.

54 The latter finding suggests a role for NCS-1 in desensitization of D2 in the prefrontal cortex.

55 Frequenin/NCS-1 has been shown to enhance exocytotic activity in a

56 Furthermore, NCS-1 did not alter the insulin-stimulated protein kinas

57 to NCS-1 shifted titration curves to higher NCS-1 concentrations, suggesting that the binding of NCS

58 When cells were stimulated with histamine, NCS-1 overexpression led to higher exocytosis, as well a

59 To better understand how NCS-1 regulates stimulus-secretion coupling, bovine chro

60 ing proteins on Kv4 channel gating, however, NCS-1 co-expression does not measurably affect the volta

61 omyces cerevisiae frequenin (Frq1) and human NCS-1 is also reflected at the functional level.

62 Expression of human NCS-1 in yeast, but not a close relative (human KChIP2),

63 and Ca(2+)-induced conformational changes in NCS-1 as compared with the role in the nonmyristoylated

64 yristoyl-dependent conformational changes in NCS-1.

65 lished after a single amino acid mutation in NCS-1 that has been shown to impair the calcium-binding

66 activation of calpain and the reductions in NCS-1 levels and calcium signaling associated with these

67 interface and uncovers a suitable region in NCS-1 for development of additional drugs of potential u

68 to study the folding behavior of individual NCS-1 molecules in the presence of Mg(2+) and in the abs

69 on InsP3R1 function, suggesting that InsP3R1/NCS-1 interaction is an essential component of the patho

70 To determine whether InsP3R1/NCS-1 interaction could be functionally relevant in bipo

71 In the absence of divalent ions, NCS-1 unfolds and refolds reversibly in a two-state reac

72 ow D2R peptide concentrations calcium-loaded NCS-1 binds to the D2R peptide in a monomeric form.

73 her observed that short hairpin RNA-mediated NCS-1 knockdown had a similar effect on phosphoinositide

74 Moreover, NCS-1 showed partial colocalization with GLUT4-EGFP in t

75 Mutant NCS-1 does not inhibit surface-expression of TRPC5 but g

76 (3) N-Terminally myristoylated NCS-1 dimerizes in a calcium-dependent manner.

77 ee of cooperativity; thus, the myristoylated NCS-1 binds Ca(2+) more strongly (with three Ca(2+) bind

78 activity was blocked by a dominant-negative NCS-1 construct.

79 nt protein imaging show that KChIPs (but not NCS-1) effectively bind to Kv4.3 protein and localize at

80 The ability of NCS-1 to modulate D2 receptor signaling was abolished af

81 In the absence of NCS-1, worms show delayed onset and a shorter duration o

82 The inhibitory action of NCS-1 was independent of calcium sequestration since nei

83 is known that the physiological activity of NCS-1 is governed by its myristoylation.

84 ncentrations, suggesting that the binding of NCS-1 to the D2R is highly specific and that binding occ

85 Taxol increased binding of NCS-1 to the inositol 1,4,5-trisphosphate receptor.

86 The data also show the coexistence of NCS-1 and D2 at the ultrastructural level.

87 Colocalization of NCS-1 and D2 receptors was examined in both primate and

88 rminal helix inside a hydrophobic crevice of NCS-1 to impede Ric8a interaction.

89 cells from paclitaxel-induced degradation of NCS-1 by inhibiting calpain activity.

90 nduces activation of calpain, degradation of NCS-1, and loss of intracellular calcium signaling.

91 u-calpain, which leads to the degradation of NCS-1, which, in turn, attenuates InsP(3)mediated Ca(2+)

92 tochemistry showed a similar distribution of NCS-1 and phosphatidylinositol 4-kinase beta (PI4Kbeta).

93 for the target specificity and diversity of NCS-1.

94 Lithium inhibited the enhancing effect of NCS-1 on InsP3R1 function, suggesting that InsP3R1/NCS-1

95 This effect of NCS-1 was accompanied by an increase in D2 receptor-medi

96 The effect of NCS-1 was specific for GLUT4 and the insulin-responsive

97 We demonstrate antagonist effects of NCS-1 and ARF on constitutive and regulated exocytosis.

98 Expression of NCS-1 (neuronal calcium sensor-1, also termed frequenin)

99 Co-expression of NCS-1 also decreases the rate of inactivation of Kv4 alp

100 We examined the expression of NCS-1 in the developing and mature olfactory system to d

101 During development, expression of NCS-1 in the olfactory epithelium was localized in the d

102 In intact cells, enhanced expression of NCS-1 resulted in increased intracellular calcium releas

103 We propose, therefore, that the function of NCS-1 in mammals may closely resemble that of Frq1 in S.

104 Short hairpin RNA-mediated knockdown of NCS-1 in the same cell line abrogated the response to ta

105 antia nigra dopamine messenger RNA levels of NCS-1 (but not Cav1.2 or Cav1.3) after cocaine in mice,

106 site of NCS-1 to decrease the likelihood of NCS-1 degradation.

107 consistent with the genetic manipulation of NCS-1.

108 lus NCS-1, except that the overexpression of NCS-1 resulted in a faster rundown in exocytosis.

109 fluorescence anisotropy (FA) and a panel of NCS-1 EF-hand variants to interrogate the interaction be

110 sults allowed us to trace the progression of NCS-1 folding along its energy landscapes and provided a

111 to impair the calcium-binding properties of NCS-1.

112 2R peptide binds to the first 60 residues of NCS-1.

113 ta suggest multiple and overlapping roles of NCS-1 in the developing and mature olfactory system.

114 P2 position of the calpain cleavage site of NCS-1 to decrease the likelihood of NCS-1 degradation.

115 made possible by the C-lobe-binding site of NCS-1, which adopts alternative conformations in each co

116 Under tension, the Mg(2+)-bound state of NCS-1 unfolds and refolds in a three-state process by po

117 The crystal structure of NCS-1 bound to FD44 and the structure-function studies p

118 Expression of either mutated version of NCS-1 in neuroblastoma cells protected intracellular cal

119 Next, we tested two mutated versions of NCS-1 developed with point mutations at the P2 position

120 green fluorescent protein (GFP) or GFP plus NCS-1, except that the overexpression of NCS-1 resulted

121 Mutants with defects in four potential NCS-1 targets (arf-1.1, pifk-1, trp-1 and trp-2) showed

122 ng that the NCS-1 C-terminal region prevents NCS-1 oligomerization.

123 ves the neuronal Ca(2+) sensor (NCS) protein NCS-1.

124 orest virus (SFV) vectors containing the rat NCS-1 gene.

125 ase activity when incubated with recombinant NCS-1, but only if the latter was myristoylated.

126 e interaction of the neuronal calcium sensor NCS-1 with D2-autoreceptors.

127 In striatum, NCS-1 and D2 receptors were found to colocalize within s

128 expressed in adult mouse ventricles and that NCS-1 co-immunoprecipitates with Kv4.3 from (adult mouse

129 pitation experiments in HEK-293 confirm that NCS-1 can oligomerize in cell lysates and that oligomeri

130 We also found that NCS-1 is readily degraded by mu-calpain in vitro and tha

131 These results together indicate that NCS-1 is able to interact with PI4Kbeta also in mammalia

132 an embryonic kidney 293 cells indicates that NCS-1 attenuates agonist-induced receptor internalizatio

133 uency trains of stimulation, indicating that NCS-1 can recruit 'dormant' vesicles.

134 ression studies in HEK-293 cells reveal that NCS-1 increases membrane expression of Kv4 alpha-subunit

135 xperiments from striatal neurons reveal that NCS-1 is found in association with both the D2 receptor

136 g(2+) FA titration experiments revealed that NCS-1 EF-hands 2-4 (EF2-4) contributed to binding with t

137 We show that NCS-1 can exert bidirectional effects to activate PI(4)K

138 Our results suggest that NCS-1 acts as a calcium sensor for short-term plasticity

139 Taken together, these results suggest that NCS-1 is an accessory subunit of Kv4-encoded I(to,f) cha

140 These results suggest that NCS-1 may regulate cellular activity through the modulat

141 The NCS-1-ARF1 interaction and its specificity have been dem

142 The NCS-1-ARF1 interaction provides evidence for functional

143 Furthermore, the NCS-1-PICK1 association is stimulated by activation of m

144 In contrast, expression of the NCS-1 effector phosphatidylinositol 4-kinase (PI 4-kinas

145 We determined NMR structures of the NCS-1 homolog from fission yeast (Ncs1), which activates

146 ient to promote high-affinity binding of the NCS-1 monomer to the D2R peptide.

147 all molecules as potential inhibitors of the NCS-1/Ric8a interaction.

148 Our study shows the drugability of the NCS-1/Ric8a interface and uncovers a suitable region in

149 d the large hydrophobic crevice based on the NCS-1 crystal structure, this crevice may be the associa

150 an inactive PI 4-kinase mutant prevented the NCS-1-induced inhibition.

151 ant that formed a dimer, indicating that the NCS-1 C-terminal region prevents NCS-1 oligomerization.

152 Thus, NCS-1 plays a distinct role in mGluR-LTD.

153 compete with labeled peptide for binding to NCS-1 shifted titration curves to higher NCS-1 concentra

154 Similarly, in vitro translated NCS-1, but not its myristoylation-defective mutant, was

155 y a model in which the D2R peptide binds two NCS-1 monomers sequentially in a cooperative fashion.

156 When NCS-1 protein levels recovered, so did InsP(3)-mediated

157 nt in bipolar disorders, conditions in which NCS-1 is highly expressed, we tested the effect of lithi

158 aved more favorably by calpain compared with NCS-1 WT, whereas the other mutant was less favorably cl

159 d an intermediate phenotype, consistent with NCS-1 and ARF-1.1 acting in the same pathway.

160 4 translocation through its interaction with NCS-1.

161 findings suggest that ARF-1.1 interacts with NCS-1 in AIY neurons and potentially pifk-1 in the Ca(2+

162 The aminophenothiazine FD44 interferes with NCS-1/Ric8a binding, and it restores normal synapse numb