ライフサイエンスコーパス: STIM2

1 eveals direct interactions between STIM1 and STIM2.

2 endoplasmic reticulum (ER) sensors STIM1 and STIM2.

3 -depletion-mediated Ca(2+) influx, STIM1 and STIM2.

4 Ca(2+) channel-associated proteins Stim1 and Stim2.

5 ndoplasmic reticulum Ca2+ sensors, STIM1 and STIM2.

6 tes AMPK colocalization and interaction with STIM2.

7 nd stromal interaction protein 1 (STIM1) and STIM2.

8 entry is mediated exclusively by endogenous STIM2.

9 by stromal interaction molecule (STIM) 1 and STIM2.

10 by stromal interaction molecule (STIM) 1 and STIM2.

11 way is controlled by the ER resident protein STIM2.

12 max channels are activated by both STIM1 and STIM2.

13 doplasmic reticulum Ca(2+) sensors STIM1 and STIM2.

14 -Orai-activating regions (SOAR) of STIM1 and STIM2.

15 essential role of STIM1 partially rescued by STIM2.

16 ceptor-mediated depletion of ER Ca2+ stores, STIM2 activated Ca2+ influx upon smaller decreases in ER

17 ructural properties distinguishing STIM1 and STIM2 activation of ORAI1 channels under native conditio

18 y is required for specific store-independent STIM2 activation.

19 In the absence of STIM1 and STIM2, acute viral infections became chronic.

20 and attenuated the association of Orai1 with STIM2 and AKAP79.

21 Downregulation requires Stim1/Stim2 and CaMK4 expression and involves Arpp21 protein p

22 +) entry is mediated initially by endogenous STIM2 and incrementally by STIM1, enabling differential

23 Changes in the ratio between active STIM2 and STIM1 proteins can switch the regulation of Im

24 gene expression through recruitment of both STIM2 and STIM1.

25 amate release through a pathway dependent on STIM2 and the synaptic Ca(2+) sensor synaptotagmin-7 (sy

26 new data about cross-talk between STIM1 and STIM2 and their different roles in store-operated channe

27 we used CRISPR/Cas9 to generate STIM1(-/-), STIM2(-/-), and STIM1/2(-/-) knockouts in HEK293 and col

28 etermines IP(3)R function, immobilization of STIM2, and basal Ca(2+) entry while agonist stimulation

29 Together, our data indicate that STIM1, STIM2, and CRAC channel function play distinct but syner

30 n KGM-H display enhancement of Orai1, STIM1, STIM2, and nuclear factor of activated T cells 1 (NFAT1)

31 Our findings demonstrate that STIM1, STIM2, and SOCE are dispensable for many critical effect

32 phology, in part due to its association with STIM2, and that modulation of EB3 expression is a potent

33 generate smooth muscle (sm)-targeted STIM1-, STIM2-, and double STIM1/STIM2-knockout (KO) mouse model

34 STIM1 and STIM2 are calcium-sensing molecules that link calcium de

35 STIM1 and STIM2 are dynamic transmembrane endoplasmic reticulum Ca

36 STIM1 and STIM2 are widely expressed endoplasmic reticulum (ER) Ca

37 mal interaction molecules 1 and 2 (STIM1 and STIM2) are key modulators of store-operated calcium entr

38 Stromal interaction molecules (STIM1 and STIM2) are single pass transmembrane proteins located ma

39 ors, stromal interaction molecules STIM1 and STIM2, are key regulators of cancer cell migration.

40 kdown approach, we identified both STIM1 and STIM2 as important mediators of SOCE and SOC current, an

41 lators of basal Ca2+ concentration and found STIM2 as the strongest positive regulator.

42 Our study places STIM2 at the center of a feedback module that keeps basa

43 43-amino-acid STIM1 N terminus with that of STIM2 attenuates Orai1-mediated Ca(2+) entry and drastic

44 issue, Militsin et al. reveal how STIM1 and STIM2-beyond their typical role as ER Ca2+ sensors that

45 ver, neutrophil cytokine production required STIM2, but not STIM1, at least in part as a result of re

46 basophils were stimulated with IL-3, loss of STIM2, but not STIM1, reduced basophil IL-4 production.

47 e, we demonstrated that reduced abundance of STIM2, but not that of STIM1, was associated with poor p

48 Molecular silencing of STIM2 by siRNA or inhibition by G418 suppresses store-op

49 e show that the increased flexibility of the STIM2 C terminus contributes to its selective store-inde

50 We show that depending on cell type, STIM2 can significantly sustain SOCE in response to maxi

51 STIM1/STIM2 chimeric constructs indicated that coordination be

52 The cellular cues that determine STIM2 clustering under basal conditions is not known.

53 ER-PM junctions, but are not sufficient for STIM2 clustering.

54 We show that immobile STIM2 clusters denote decreases in local [Ca(2+)](ER) me

55 , our findings reveal that immobilization of STIM2 clusters within ER-PM junctions, a first response

56 Agonist stimulation increases immobile STIM2 clusters, which coordinate recruitment of Orai1 an

57 onding increase, or attenuation, of immobile STIM2 clusters.

58 Ca(2+)](ER) are the main drivers of immobile STIM2 clusters.

59 Independent of store depletion, STIM2 colocalizes with and blocks the function of a STIM

60 -terminal random coil sequences of STIM1 and STIM2 confer profoundly different activation properties.

61 Here we report that while both STIM1 and STIM2 contribute to store-refilling during Ca(2+) oscill

62 onclude that a reciprocal shift in TRPC1 and STIM2 contributes to Ca(2+) remodeling and tumor feature

63 and CaM regulation, which indicates that the STIM2/CRACM1 complex may be under the control of both lu

64 n (KD) of obligate calcium sensors STIM1 and STIM2 decreased the magnitude of muscarinic agonist indu

65 We further show that STIM2 deficiency attenuates calcium-induced but not ener

66 STIM2 deficiency in CRC xenografts led to increased tumo

67 STIM2-deficient CRC cells showed enhanced ER Ca(2+) cont

68 Transcriptional profiling of STIM1/STIM2-deficient Treg cells reveals that Ca(2+) signaling

69 is a highly specific and potent inhibitor of STIM2-dependent CRAC channel activation.

70 suggest EVP4593 and other inhibitors of the STIM2-dependent nSOC pathway as promising leads for HD t

71 , contributes to synaptotoxic enhancement of STIM2-dependent store-operated calcium (SOC) entry.

72 scued loss of mushroom spines resulting from STIM2 depletion.

73 ) T(reg) cell-specific deletion of Stim1 and Stim2 develop a phenotype that fulfills all classificati

74 he results of this study show that STIM1 and STIM2 differ in the ability to activate these store-oper

75 esponds when [Ca(2+)](ER) is relatively low, STIM2 displays constitutive clustering in the junctions

76 of Stromal Interaction Molecule (STIM) 1 and STIM2 [double-knockout (DKO)] mice develop spontaneous a

77 tional S1ct-Orai1 coupling occurred in STIM1/STIM2(-/-) DT40 chicken B cells, indicating ct fragments

78 e-Pro aminoacid motif and that disruption of STIM2-EB3 interaction resulted in loss of mushroom spine

79 PIP(2)-binding domain of STIM1 with that of STIM2 eliminated the requirement of STIM2 for NFAT1 acti

80 ucine-replacement of this crucial residue in STIM2 endows it with partial agonist properties, which m

81 Knockdown of STIM2 expression had relatively little effect on Orai1/S

82 We discovered that STIM2 expression is elevated in aged YAC128 striatal cul

83 In addition, STIM2 expression was necessary to maintain the frequency

84 that of STIM2 eliminated the requirement of STIM2 for NFAT1 activation.

85 We showed that STIM2 forms an endoplasmic reticulum (ER) Ca(2+) -depend

86 Although structurally homologous, STIM1 and STIM2 generate distinct Ca(2+) signatures in response to

87 Here we show that deletion of Stim1 and Stim2 genes in mature Treg cells abolishes Ca(2+) signal

88 Conditional deletion of Stim1 and Stim2 genes in T cells abolished SOCE and strongly reduc

89 mice with conditional deletion of Stim1 and Stim2 genes, and therefore complete inhibition of SOCE,

90 ux, whereas deficiency in the calcium sensor STIM2 had a smaller effect.

91 However, T cells lacking either STIM1 or STIM2 had much less cytokine production and nuclear tran

92 Here we reveal that STIM2 has two distinct modes of activating CRAC channels

93 These data indicate that STIM1 and STIM2 have differential roles in the production of IL-4,

94 We found that loss of STIM1, but not STIM2, impaired basophil IL-4 production after stimulati

95 , these results illustrate the vital role of STIM2 in basophils, which is often considered to be less

96 D8+ T cells required expression of STIM1 and STIM2 in CD4+ T cells.

97 these data demonstrate an important role for STIM2 in coupling Orai1-mediated Ca(2+) influx to NFAT1

98 inct but cooperative functions for STIM1 and STIM2 in modulating neutrophil bactericidal and cytokine

99 tim1 and/or Stim2 to investigate the role of STIM2 in neutrophil activation.

100 this study, we examined the contribution of STIM2 in NFAT1 activation.

101 onditional deletion of Stim1 and its homolog Stim2 in T cells, we determined that both components are

102 by stromal interaction molecule (STIM)1 and STIM2 in the endoplasmic reticulum.

103 In the absence of STIM1/STIM2 in Treg cells, mice develop a broad spectrum of au

104 omal interaction molecule 1 and 2 (STIM1 and STIM2), in basophil activation.

105 tiated by calcium sensor proteins, STIM1 and STIM2, in the endoplasmic reticulum [3].

106 Only a few studies have recorded STIM2-induced CRAC (calcium release-activated calcium) c

107 The close STIM1 homologue, STIM2, inhibited SOCE when expressed alone but coexpress

108 We reveal that STIM2 interacts with AMPK and CaMKK2 and that the increa

109 STIM2 interacts with AMPK and regulates calcium-induced

110 M1 is a required mediator of SOC activation, STIM2 is a powerful inhibitor of this process, interferi

111 We reveal that STIM2 is a powerful SOC inhibitor when expressed in HEK2

112 When compared with STIM1, STIM2 is a weak activator of Orai1, but it has been sugg

113 STIM2 is activated by changes in endoplasmic reticulum c

114 hannels, but it has remained unclear whether STIM2 is capable of regulating store-operated non-CRAC c

115 endogenous STIM2, we report that endogenous STIM2 is constitutively localized in mobile and immobile

116 xpressed in both the ER and plasma membrane, STIM2 is expressed only intracellularly.

117 omal interacting molecule 1 (STIM1), whereas STIM2 is mainly confined to the outer plexiform and RGC

118 Thus, STIM2 is preferentially activated by low-level physiolog

119 press SOCE-mediated spontaneous release, and STIM2 is required for the increase in spontaneous releas

120 vation has been established, the function of STIM2 is unknown.

121 y stromal interacting molecule 1 (STIM1) and STIM2, is the main Ca2+ influx pathway triggered by BCR

122 in the frequency of calcium oscillations and STIM2 KD reduced spontaneous OPC differentiation.

123 In addition, STIM2 knockdown decreases SOCE and Ca(2+) store content

124 m)-targeted STIM1-, STIM2-, and double STIM1/STIM2-knockout (KO) mouse models, which reveal the essen

125 While sm-STIM2-KO was without detectable phenotype, the STIM1/STI

126 STIM2, like STIM1, caused Ca2+ influx via activation of

127 STIM2 loss activated the expression of genes involved in

128 These results suggest that loss of STIM2 may inform CRC prognosis.

129 These data suggest that loss of STIM2 may underlie Ca(2+) store depletion and apoptosis

130 stabilization of mushroom spines depends on STIM2-mediated neuronal store-operated calcium influx (n

131 ER) mediated by IP(3)R that is sensed by the STIM2 N terminus.

132 We demonstrate that STIM2-nSOC-CaMKII pathway is compromised in KI neurons,

133 Our results identify STIM2-nSOC-CaMKII synaptic maintenance pathway as a nove

134 Knockdown of STIM1, STIM2 or Orai1 decreased resting Ca(2+) levels.

135 Knockdown of Stim1, Stim2, or Orai1 inhibited EC proliferation and caused ce

136 ic VSMC proliferation and migration, whereas STIM2, Orai2, and Orai3 knockdown had no effect.

137 STIM2 overexpression failed to restore mushroom dendriti

138 ctive activation of native STIM2 proteins or STIM2 overexpression results in store-operated activatio

139 We conclude that both STIM1 and STIM2 promote store-operated Ca2+ entry into T cells and

140 7]; however, the role of the closely related STIM2 protein remains undetermined.

141 In contrast, STIM2 protein was nearly depleted in tumor cells.

142 nSOC) in hippocampal neurons is regulated by STIM2 protein.

143 sporadic AD brains due to downregulation of STIM2 protein.

144 previously unreported link between STIM1 and STIM2 proteins and pSS.

145 Thus, deficiency of STIM1 and STIM2 proteins in T cells, and consequent defects in Ca(

146 HEK293 cells, selective activation of native STIM2 proteins or STIM2 overexpression results in store-

147 nstrated significant reductions in STIM1 and STIM2 proteins.

148 Knockdown of PKCdelta with siRNA increased STIM2 punctum formation and enhanced basal calcium entry

149 We report that STIM2 recruitment of Orai1/STIM1 to ER-PM junctions in r

150 nce for the existence of endogenous non-CRAC STIM2-regulated channels.

151 d in pathology, but available data on native STIM2-regulated plasma membrane channels are scarce.

152 endoplasmic reticulum (ER), the function of STIM2 remains unclear.

153 We further establish that overexpression of STIM2 rescues synaptic nSOC, CaMKII activity, and mushro

154 T cell-specific ablation of both STIM1 and STIM2 resulted in a notable lymphoproliferative phenotyp

155 igonucleotides or knock-down or knock-out of STIM2 resulted in normalization of nSOC and rescue of sp

156 We demonstrate that loss of STIM2 results in decreased SOCE, particularly at lower d

157 In vivo loss of STIM2 results in lower cytokine levels and protection fr

158 cytoplasmic C-terminal domains of STIM1 and STIM2 (S1ct and S2ct) and identifying a fundamental acti

159 STIM1 and STIM2 sense the depletion of ER Ca(2+) stores, whereas O

160 Stromal interaction molecules, STIM1 and STIM2, sense decreases in the endoplasmic reticulum (ER)

161 independent of ER Ca(2+) stores or STIM1 and STIM2 sensors and uncoupled from Ca(2+)-ATPase activity

162 romal cell-interaction molecule (STIM) 1 and STIM2 serve as endoplasmic reticulum Ca(2+) sensors that

163 KO of either STIM1 or STIM2 significantly reduces CRAC channel activity.

164 Furthermore, STIM2 siRNA prevented the effects of muscarinic agonist

165 deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal swe

166 The opposing functions of STIM1 and STIM2 suggest they may play a coordinated role in contro

167 nd phagocytosis are normal in the absence of STIM2, suggesting STIM1 is the dominant calcium sensor r

168 As such, STIM1 and STIM2 synergize for optimal Ca(2+) oscillations and acti

169 Conversely, the 55-amino-acid STIM2 terminus substituted within STIM1 strikingly enhan

170 show that, surprisingly, it is STIM1 and not STIM2 that is exclusively involved in calcium entry duri

171 a novel bimodal control of CRAC channels by STIM2, the store dependence and CaM regulation, which in

172 powerful coupling modifiers, functioning in STIM2 to "brake" the otherwise constitutive activation o

173 ce with conditional ablation of Stim1 and/or Stim2 to investigate the role of STIM2 in neutrophil act

174 istribution of STIM1 into distinct "puncta." STIM2 translocates into puncta upon store depletion only

175 ted channels; Imin channels are regulated by STIM2, TRPC3-containing INS channels are induced by STIM

176 ronic allergic inflammation in vivo, whereas STIM2 was required for IL-4 production after combined IL

177 an eight-residue-inserted splice variant of STIM2, was found to act as an inhibitor of SOCE.

178 gene editing to fluorescently tag endogenous STIM2, we report that endogenous STIM2 is constitutively

179 Early during infection, STIM1 and STIM2 were required for the differentiation of naive CD8

180 CD4+ T cells lacking STIM1 and STIM2 were unable to provide "help" to CD8+ T cells due

181 f CRAC channels (ORAI1, ORAI2, ORAI3, STIM1, STIM2) were expressed and most abundant during the matur

182 s stromal interaction molecule 1 (STIM1) and STIM2, which transition into an active conformation in r

183 T1 activation were recovered by coexpressing STIM2 with STIM1DeltaK.

184 d by stromal interaction molecules STIM1 and STIM2 within endoplasmic reticulum (ER)-plasma membrane

185 uble labeling shows coincidence of STIM1 and STIM2 within puncta, and immunoprecipitation reveals dir