ライフサイエンスコーパス: PtdSer

1 is uniquely enriched in phosphatidylserine (PtdSer).

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

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

4 1 that reduced host cell surface exposure of PtdSer.

5 come activated by apoptotic cells expressing PtdSer.

6 entation, resulting in marked endocytosis of PtdSer.

7 paired with a polyunsaturated fatty acid to PtdSer.

8 ostatic contacts with acidic lipids, such as PtdSer.

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

10 1 is also a receptor for phosphatidylserine (PtdSer), an important marker of cells undergoing program

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

53 hatidylethanolamine formation despite normal PtdSer decarboxylase 2 activity.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

69 membrane tension minimized invagination and PtdSer endocytosis.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

89 PtdSer liposomes but not phosphatidylcholine liposomes c

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

119 The PtdSer receptors human and murine T-cell immunoglobulin

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

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

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

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

124 cytoplasmic tail promoted corpse uptake via PtdSer recognition.

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

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

127 PtdSer structure was controlled by the substrate specifi

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

145 PtdSer transfer is also dependent upon both the bulk and

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

147 orming a zone of apposition that facilitates PtdSer transfer.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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