ライフサイエンスコーパス: PtdSer

1 fundamental of which is phosphatidylserine (PtdSer).

2 reased surface levels of phosphatidylserine (PtdSer).

3 its membrane anchor and phosphatidylserine (PtdSer).

4 hat specifically engages phosphatidylserine (PtdSer).

5 is uniquely enriched in phosphatidylserine (PtdSer).

6 h as PtdIns(4,5)P(2) and phosphatidylserine (PtdSer).

7 ostatic contacts with acidic lipids, such as PtdSer.

8 dering of the acyl chains of both PtdCho and PtdSer.

9 entation, resulting in marked endocytosis of PtdSer.

10 lation of junctional PI(4)P, PI(4,5)P(2) and PtdSer.

11 dging protein that is independently bound to PtdSer.

12 1 that reduced host cell surface exposure of PtdSer.

13 come activated by apoptotic cells expressing PtdSer.

14 paired with a polyunsaturated fatty acid to PtdSer.

15 Therefore, depleting PM PtdSer abrogates KRAS PM binding and activity.

16 In addition, CD36 appears to be specific for PtdSer among anionic phospholipids, and non-phospholipid

17 1 is also a receptor for phosphatidylserine (PtdSer), an important marker of cells undergoing program

18 monstrates a 50% increase in the labeling of PtdSer and a 72% decrease in PtdEtn formation in the mut

19 ed a mutant, denoted pstB1, that accumulates PtdSer and has diminished phosphatidylethanolamine forma

20 synthesis, promoting the PM localization of PtdSer and KRAS.

21 ors disrupt the PM localization of K-Ras and PtdSer and oncogenic K-Ras signaling.

22 osed as one receptor protein that recognizes PtdSer and other anionic phospholipids.

23 Finally, the localized presentation of PtdSer and other eat-me signals on delimited cell surfac

24 followed the metabolism of [(3)H]serine into PtdSer and PtdEtn to study lipid transport in permeabili

25 of agents targeting the interaction between PtdSer and TIM-3 in the realm of cancer immunotherapy.

26 The permeabilized cells synthesize (3)H-PtdSer and, after a 20-min lag, decarboxylate it to form

27 M inhibitor, reduces the phosphatidylserine (PtdSer) and cholesterol content of the inner plasma memb

28 s and H-Ras by depleting phosphatidylserine (PtdSer) and cholesterol contents, respectively, at the i

29 le by decarboxylation of phosphatidylserine (PtdSer) and in the endoplasmic reticulum by fusion of CD

30 l relevance, can salvage phosphatidylserine (PtdSer) and phosphatidylethanolamine (PtdEtn) but not ph

31 Phosphatidylserine (PtdSer) and phosphatidylinositol 4,5-bisphosphate (PtdIn

32 membrane lipids (mainly phosphatidylserine (PtdSer) and phosphoinositides (PtdIns)) but the molecula

33 totagmin-1 into the membrane, via binding of PtdSer, and an increase in the affinity of the polybasic

34 to form nanodomains where the headgroups of PtdSer are maintained sufficiently separated to limit sp

35 These findings reveal a role of PtdSer as a signaling lipid that controls the available

36 mbranes containing either 100% PtdSer or 50% PtdSer at a fixed concentration (e.g. 250 microM PtdSer)

37 amblases whose action results in exposure of PtdSer at the cell surface.

38 e show selective translocation of PtdEtn and PtdSer at the parasite surface and provide the underlyin

39 he signal transduction needed to internalize PtdSer-bearing targets such as apoptotic cells.

40 ch rendered them competent for engulfment of PtdSer-bearing targets.

41 formation of the PtdCho headgroups in PtdCho/PtdSer bilayers indicated that positively charged residu

42 onents was similar to the case of the PtdCho/PtdSer bilayers, histone did not significantly affect th

43 The results showed that in PtdCho/PtdSer bilayers, histone preferentially increased order

44 While it is known that the PtdSer binding is essential for the PVEER function of TI

45 that of TIM-4/PtdSer, reflecting a conserved PtdSer binding mode by TIM family members.

46 Similar to TIM-1, residues in the PtdSer binding pocket of murine and human TIM-4 (mTIM-4

47 PtdSer on the virion surface via a conserved PtdSer binding pocket within the amino-terminal IgV doma

48 Our findings provide a role for the PtdSer binding site and its previously unrewarding role

49 Here, we showed that key phosphatidylserine (PtdSer) binding residues of the TIM-1 IgV domain are cri

50 ucin protein 4 (TIM4), a phosphatidylserine (PtdSer)-binding receptor, mediates the phagocytosis of a

51 hosphatidylserine (PtdSer): Gas6 lacking its PtdSer-binding 'Gla domain' is significantly weakened as

52 The PtdSer-binding activity of the immunoglobulin-like varia

53 s, we found that in addition to a functional PtdSer-binding domain PVEERs require a stalk domain of s

54 ct was entirely abolished by addition of the PtdSer-binding protein, annexin V, confirming that it wa

55 vide evidence for a broad role of TIM-1 as a PtdSer-binding receptor that mediates enveloped-virus up

56 coprotein, providing evidence that TIM-1 and PtdSer-binding receptors can mediate virus uptake indepe

57 Utilization of PtdSer-binding receptors may explain the wide tropism of

58 tive by small molecules that drive it to its PtdSer-bound conformer.

59 d order parameters of the acyl chains of the PtdSer, but not the PtdCho lipid component.

60 Surface dilution of PtdSer by choline, ethanolamine, glycerol, and inositol

61 In yeast, nascent phosphatidylserine (PtdSer) can be transported to the mitochondria and Golgi

62 s in the interactions of histone with PtdCho/PtdSer compared with PtdCho/PtdGro bilayers may explain

63 physiological functions; however, junctional PtdSer composition and the role of PtdSer in Ca(2+) sign

64 at anti-inflammatory signals can be given by PtdSer-containing cell membranes, whether from early apo

65 idylserine (PtdSer)-displaying dead cells or PtdSer-containing liposomes.

66 so selectively inhibited the phagocytosis of PtdSer-containing vesicles as measured by fluorescence m

67 lete the PM-to-ER PI4P gradient, reducing PM PtdSer content.

68 ignaling capacity critically dependent on PM PtdSer content.

69 that the parasite secretes a soluble form of PtdSer decarboxylase (TgPSD1), which preferentially deca

70 hatidylethanolamine at the inner membrane by PtdSer decarboxylase 1 (Psd1p).

71 in the endoplasmic reticulum to the locus of PtdSer decarboxylase 2 (Psd2p) in the Golgi/vacuole and

72 indicator of lipid transport to the locus of PtdSer decarboxylase 2 (Psd2p) in the Golgi/vacuole.

73 s lipid to endosomes, and decarboxylation by PtdSer decarboxylase 2 (Psd2p) to produce phosphatidylet

74 hatidylethanolamine formation despite normal PtdSer decarboxylase 2 activity.

75 and its transport to and decarboxylation by PtdSer decarboxylase 2 in the Golgi/vacuole has been dev

76 Ser) to phosphatidylethanolamine (PtdEtn) by PtdSer decarboxylase 2, has been isolated.

77 t processes that control substrate access to PtdSer decarboxylase 2.

78 Deletion of both the PtdSer decarboxylase and Kennedy pathways yields a strai

79 eld PtdCho, which confirms the expression of PtdSer decarboxylase but a lack of PtdEtn methyltransfer

80 l, illustrating the complete reliance on the PtdSer decarboxylase pathway for PtdEtn synthesis.

81 ith a psd1Delta allele for the mitochondrial PtdSer decarboxylase, the conversion of nascent PtdSer t

82 ith psd1Delta psd2Delta mutations, devoid of PtdSer decarboxylases, import and acylate exogenous 1-ac

83 tuted for the TIM-1 IgV domain, supporting a PtdSer-dependent mechanism.

84 g protein, annexin V, confirming that it was PtdSer-dependent.

85 , but the consequence of TIM-3 engagement of PtdSer depends on the polymorphic variants of and type o

86 nic composition of the medium, and exogenous PtdSer did not modulate the enzyme secretion, which sugg

87 er at a fixed concentration (e.g. 250 microM PtdSer) differs by a factor of 20.

88 TIM4 receptor by either phosphatidylserine (PtdSer)-displaying dead cells or PtdSer-containing lipos

89 However, TIM-3, whose IgV domain also binds PtdSer, does not effectively enhance virus entry, indica

90 PtdSer transport involving the docking of a PtdSer donor membrane with an acceptor via specific prot

91 membrane tension minimized invagination and PtdSer endocytosis.

92 RP5, a lipid transfer protein maintaining PM PtdSer enrichment.

93 IM1-formed junctions are required for PI(4)P/PtdSer exchange by ORP5 and ORP8, which have reciprocal

94 We propose that the PtdSer exposed on the outside of these blebs can induce

95 TIM-4 are receptors for phosphatidylserine (PtdSer), exposed on the surfaces of apoptotic cells.

96 head region of viable and motile sperm, with PtdSer exposure progressively increasing during sperm tr

97 approaches revealed that phosphatidylserine (PtdSer) exposure on the outer leaflet of transduced cell

98 ntracellular calcium dysregulation, prevents PtdSer externalization, and enables months-long protecti

99 essential for E-Syt3 function, as removal of PtdSer from junctions by E-Syt3 dissociated the cAMP sig

100 Most importantly, the transfer of PtdSer from liposomes to Psd2p fails to occur in accepto

101 tor and the phospholipid phosphatidylserine (PtdSer): Gas6 lacking its PtdSer-binding 'Gla domain' is

102 Exposure of phosphatidylserine (PtdSer) has been implicated in the recognition and phago

103 NBD-PtdSer imported to the parasite interior is decarboxylat

104 ilayers may explain the higher efficiency of PtdSer in activating PKC.

105 unctional PtdSer composition and the role of PtdSer in Ca(2+) signaling and Ca(2+)-dependent gene reg

106 able PM PI(4)P, the unappreciated role of ER PtdSer in cell function, and the diversity of the ER/PM

107 ndicate that histone 1 induces clustering of PtdSer in PtdCho bilayers which may contribute to PKC ac

108 es that the pstB2 strain accumulates nascent PtdSer in the Golgi apparatus and a novel light membrane

109 critical role of enveloped-virion-associated PtdSer in TIM-1-mediated uptake, TIM-1 enhanced internal

110 significantly reduced the impact of elevated PtdSer in TMEM30A KO leukemic cells.

111 nvolves the synthesis of phosphatidylserine (PtdSer) in the endoplasmic reticulum (ER), the transport

112 emoval of cholesterol or insertion of excess PtdSer increases the charge density of the inner leaflet

113 TIM-1 recognition of PtdSer induced NKT cell activation, proliferation, and c

114 The key role of the TIM-3 - PtdSer interaction for NK cell regulation was further su

115 Since PtdSer is a potent surface procoagulant, and since there

116 ansport-dependent decarboxylation of nascent PtdSer is dependent upon the concentration of acceptor m

117 PtdSer is detected both by macrophage receptors that bin

118 The transfer of PtdSer is poor when the donor membranes have a high degr

119 Phosphatidylserine (PtdSer) is a key ligand on apoptotic cells, and recently

120 Here, we show that phosphatidylserine (PtdSer) is exposed on the head region of viable and moti

121 Phosphatidylserine (PtdSer) is transported from its site of synthesis in the

122 ORP8, which are essential for maintaining PM PtdSer levels and hence KRAS PM localization, are requir

123 s PM PI3P levels while reducing PM and total PtdSer levels.

124 secretion is governed by phosphatidylserine (PtdSer) levels in ER/PM nanodomains, specified by the an

125 sely reflected the behavior of its preferred PtdSer ligand to these same PM perturbations.

126 We now show that the PtdSer lipid transport proteins, ORP5 and ORP8, which ar

127 PtdSer liposomes but not phosphatidylcholine liposomes c

128 lity that defective cell surface exposure of PtdSer may be responsible for neurodegeneration.

129 are recently identified phosphatidylserine (PtdSer)-mediated virus entry-enhancing receptors (PVEERs

130 e recently identified as phosphatidylserine (PtdSer)-mediated virus entry-enhancing receptors (PVEERs

131 tification of the key features necessary for PtdSer-mediated enhancement of virus entry provides a ba

132 Phosphatidylserine (PtdSer) mediates various physiological functions; howeve

133 The lesion in PtdSer metabolism is consistent with a defect in interor

134 Examination of the phosphatidylserine (PtdSer) metabolism of T. gondii reveals that the parasit

135 ecognition receptor on NKT cells that senses PtdSer on apoptotic cells as a damage-associated molecul

136 ands of CD36 do not share binding sites with PtdSer on CD36.

137 ould fuse with skeletal myoblasts, requiring PtdSer on sperm and BAI1/3, ELMO2, RAC1 in myoblasts.

138 The effect of PtdSer on the junctional PI(4)P level should have multip

139 iments reveal different operational pools of PtdSer on the plasma membrane.

140 la virus (EBOV) and other viruses by binding PtdSer on the viral envelope, concentrating virus on the

141 (EBOV) entry through direct interaction with PtdSer on the viral envelope.

142 TIM-4 mediate filovirus entry by binding to PtdSer on the virion surface via a conserved PtdSer bind

143 from donor membranes containing either 100% PtdSer or 50% PtdSer at a fixed concentration (e.g. 250

144 n by E-Syt3; which was reversed by exogenous PtdSer or by PtdSer supplied by ORP5.

145 sport from planar domains highly enriched in PtdSer or in PtdSer plus PtdOH.

146 Blockade of PtdSer or the inhibitory receptor TIM-3, restored the NK

147 phatidylcholine (PtdCho)/phosphatidylserine (PtdSer), or PtdCho/phosphatidylglycerol (PtdGro) bilayer

148 sis of its major lipids, phosphatidylserine (PtdSer), phosphatidylethanolamine (PtdEtn), and phosphat

149 cytometric assay; vesicles contained 50 mol% PtdSer, phosphatidylinositol (PtdIns), or phosphatidylgl

150 ction as a rheostat that sets the junctional PtdSer/PI(4)P ratio.

151 and K-Ras4B signaling through the control of PtdSer plasma membrane content.

152 anar domains highly enriched in PtdSer or in PtdSer plus PtdOH.

153 d the composition of the phosphatidylserine (PtdSer) pool, illustrating the complete reliance on the

154 nce virus entry by binding the phospholipid, PtdSer, present on the viral membrane.

155 hylethanolamine, whereas other major lipids, PtdSer, PtdEtn, and PtdIns, remained largely unchanged.

156 with annexin V, which blocked the binding of PtdSer, PtdGro, and PtdIns vesicles to the THP-1 cells.

157 binding was observed for vesicles containing PtdSer, PtdIns, or PtdGro.

158 on of fendiline-treated cells with exogenous PtdSer rapidly restores K-Ras4A and K-Ras4B plasma membr

159 Notably, changing PI(4)P/PtdSer ratio by hydrolysis of PM or ER PtdSer with targe

160 RP5 sets low and ORP8 high junctional PI(4)P/PtdSer ratio that controls STIM1-STIM1 and STIM1-Orai1 i

161 Here, we overexpressed the PtdSer receptor BAI1 in mice lacking MerTK (Mertk (-/-)

162 g MerTK (Mertk (-/-) Bai1 (Tg) ) to evaluate PtdSer receptor compensation in vivo.

163 Loss of the PtdSer receptor Mertk is associated with apoptotic corps

164 establish a new paradigm for TIM proteins as PtdSer receptors and unify the function of the TIM gene

165 the Filoviridae family of viruses, utilizes PtdSer receptors for entry into target cells.

166 The PtdSer receptors human and murine T-cell immunoglobulin

167 Phosphatidylserine (PtdSer) receptors that are responsible for the clearance

168 gocytes express multiple phosphatidylserine (PtdSer) receptors that recognize apoptotic cells.

169 t how TIM-4 transduces signals downstream of PtdSer recognition [8].

170 igand on apoptotic cells, and recently three PtdSer recognition receptors have been identified, namel

171 ntify phosphatidylserine on viable sperm and PtdSer recognition receptors on oocytes as key players i

172 cytoplasmic tail promoted corpse uptake via PtdSer recognition.

173 d NBCe1-B PtdSer sensor domains responded to PtdSer reduction by E-Syt3; which was reversed by exogen

174 PtdSer structure is similar to that of TIM-4/PtdSer, reflecting a conserved PtdSer binding mode by TI

175 CFTR and NBCe1-B PtdSer sensor domains responded to PtdSer reduction by E

176 ess of the spatial organization of different PtdSer species to diverse PM perturbations, including tr

177 h anchor exhibited binding specificities for PtdSer species with distinct acyl chain compositions.

178 patterns with different phosphatidylserine (PtdSer) species, indicating that prenylated PBD-bilayer

179 hydrolysis of PM or ER PtdSer with targeted PtdSer-specific PLA1a1 reproduced the ORPs function.

180 The TIM-3/PtdSer structure is similar to that of TIM-4/PtdSer, ref

181 PtdSer structure was controlled by the substrate specifi

182 which was reversed by exogenous PtdSer or by PtdSer supplied by ORP5.

183 s controlled by the substrate specificity of PtdSer synthase that selectively converted phosphatidylc

184 synthesis of PtdEtn via phosphatidylserine (PtdSer) synthase/decarboxylase are auxotrophic for ethan

185 n of incubation and does not require ongoing PtdSer synthesis.

186 mining the steps between phosphatidylserine (PtdSer) synthesis in the endoplasmic reticulum and its t

187 Phosphatidylserine (PtdSer) synthesized in the endoplasmic reticulum and rel

188 l engulfment, and we propose that TIM-4 is a PtdSer tethering receptor without any direct signaling o

189 al studies that TIM-3 is also a receptor for PtdSer that binds in a pocket on the N-terminal IgV doma

190 We propose that cholesterol associates with PtdSer to form nanodomains where the headgroups of PtdSe

191 tes the critical and selective importance of PtdSer to K-Ras4A and K-Ras4B plasma membrane binding an

192 Ser decarboxylase, the conversion of nascent PtdSer to PtdEtn can serve as an indicator of lipid tran

193 The transport-dependent metabolism of PtdSer to PtdEtn occurs in permeabilized wild type yeast

194 defined donor membranes function to transfer PtdSer to the biological acceptor membranes containing P

195 reated cells rapidly relocalizes K-Ras4B and PtdSer to the plasma membrane.

196 he conversion of nascent phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn) by PtdSer d

197 The restriction of phosphatidylserine (PtdSer) to the inner surface of the plasma membrane bila

198 vide compelling evidence that interorganelle PtdSer traffic is regulated by ubiquitination.

199 stB2p, displays phosphatidylinositol but not PtdSer transfer activity, and its overexpression causes

200 PtdSer transfer is also dependent upon both the bulk and

201 and inositol phospholipids markedly inhibits PtdSer transfer, whereas phosphatidic acid (PtdOH) stimu

202 orming a zone of apposition that facilitates PtdSer transfer.

203 e designed a screen for strains defective in PtdSer transport (pstA mutants) between the endoplasmic

204 rmal Psd2p activity but fail to reconstitute PtdSer transport and decarboxylation.

205 rate that the pstA1-1 mutant is defective in PtdSer transport between the MAM and mitochondria.

206 PtdSer transport can be resolved into a two-component sy

207 gene that complements the growth defect and PtdSer transport defect of the pstA1-1 mutant is MET30,

208 These data support a model for PtdSer transport from planar domains highly enriched in

209 together, these results support a model for PtdSer transport involving the docking of a PtdSer donor

210 We conclude that the cellular ER-to-PM PtdSer transport mechanism is essential for KRAS PM loca

211 atasets revealed that all components of this PtdSer transport mechanism, including the PM-localized E

212 branes isolated from a previously identified PtdSer transport mutant, pstB2, contain normal Psd2p act

213 protein motifs are known to be required for PtdSer transport to occur, namely the Sec14p homolog Pst

214 ays a direct role in membrane docking and/or PtdSer transport to the enzyme.

215 rface concentrations of the lipid, with pure PtdSer vesicles acting as the most efficient donors at a

216 blocked up to 60% of the specific binding of PtdSer vesicles but had minimal to no effect on the bind

217 responsible for the high affinity binding of PtdSer vesicles to these monocyte-like cells.

218 ne (to 1 mM) had no effect on the binding of PtdSer vesicles, indicating that high affinity binding r

219 CD36, were unable to inhibit the binding of PtdSer vesicles.

220 hich preferentially decarboxylates liposomal PtdSer with an apparent K(m) of 67 muM.

221 I(4)P/PtdSer ratio by hydrolysis of PM or ER PtdSer with targeted PtdSer-specific PLA1a1 reproduced t