ライフサイエンスコーパス: LPL

1 LPL hydrolyzes triacylglycerol, which increases local su

2 LPL is also present in the brain, where its function has

3 LPL is secreted by parenchymal cells into the interstiti

4 LPL polymorphisms and triglycerides were determined and

5 LPL was required for the transition from prealveolar mac

6 LPL(-/-) mice demonstrated a very early clearance defect

7 LPL(-/-) mice exhibited a defective Ab response to Strep

8 LPL, GCKR, and APOA5 polymorphisms fit dominant, recessi

9 acid substitutions, C418Y and E421K, abolish LPL binding to GPIHBP1, suggesting that the C-terminal p

10 th chylomicronemia, C418Y and E421K, abolish LPL's ability to bind to GPIHBP1 without interfering wit

11 Both mutations abolish LPL transport across endothelial cells by GPIHBP1.

12 tutions in GPIHBP1's Ly6 domain that abolish LPL binding lead to protein dimerization/multimerization

13 09 with any of 8 other amino acids abolished LPL binding-and often did so without promoting the forma

14 2, and SIRT1) and lipogenesis (SREBP1c, ACC, LPL, and FASN).

15 ne of LPL that catalytically converts active LPL dimers into inactive monomers.

16 Adipoq-LPL mice also have increased energy expenditure.

17 These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well

18 higher in the epididymal fat pads of Adipoq-LPL mice than control mice.

19 ept for one important difference, the Adipoq-LPL mice did not gain more fat mass on HFD than control

20 ) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to red

21 as adiponectin in the adipose of the Adipoq-LPL mice, suggesting that increasing adipose tissue LPL

22 eased adiponectin serum levels in the Adipoq-LPL mice.

23 duces diet-induced obesity without affecting LPL activity.

24 Although LPL and the N-terminal domain formed a tight but short l

25 found that GIP stimulated the PKB/LKB1/AMPK/LPL pathway and fatty acid uptake only in Retn(+/+) adip

26 We also generated an LPL construct with an in-frame deletion of the N-termina

27 Our data showed that an LPL 3' UTR luciferase reporter carrying the rs13702 majo

28 the level of plasma triglycerides through an LPL-independent mechanism.

29 ross capillary endothelial cells and anchors LPL to the capillary wall during lipolysis.

30 Because both ABCG1 and LPL are expressed in adipose tissue, we hypothesized tha

31 Comparison of the APOC3 and LPL associations revealed that APOC3 association results

32 ding intravascular lipolysis and GPIHBP1 and LPL mutations causing familial chylomicronemia.

33 Moreover, PBL and LPL from most patients with active IBD failed to respond

34 ond to F. prausnitzii in contrast to PBL and LPL from patients in remission and/or healthy donors.

35 Rgamma co-occupancy observed on PGC1beta and LPL gene regulatory regions identified.

36 maH2A.X expression in colonic epithelium and LPLs confirmed the contribution of DNA damage response i

37 significantly in both colonic epithelium and LPLs.

38 , whereas minor alleles of ADIPOR2, ANGPTL3, LPL, and TRIB1 polymorphisms were inversely associated.

39 As LPL may be a target of the commonly used immunosuppressi

40 rders that have some of the same features as LPL, and healthy donors.

41 aking into consideration data that associate LPL mutations with Alzheimer's disease, a role for LPL i

42 Intriguingly, astrocytic LPL deficiency also triggered increased ceramide content

43 Likewise, astrocytic LPL deletion reduced the accumulation of lipid droplets

44 ons for lipid levels change were detected at LPL, TRIB1, APOA1-C3-A4-A5, LIPC, CETP, and LDLR (P rang

45 fast on- and off-rates, the complex between LPL and the Ly6 domain formed more slowly and persisted

46 udies showed that only GPIHBP1 monomers bind LPL.

47 GPIHBP1-W109S lacked the ability to bind LPL but had a reduced propensity for forming dimers or m

48 The ability of GPIHBP1 to bind LPL depends on the Ly6 domain, a three-fingered structur

49 n the cell surface and their ability to bind LPL were assessed with an immunofluorescence microscopy

50 109 might play a more direct role in binding LPL.

51 only GPIHBP1 monomers are capable of binding LPL.

52 t dimers or multimers-are capable of binding LPL.

53 the entry of LPL into capillaries, blocking LPL-mediated triglyceride hydrolysis and leading to mark

54 in inactivating both free and GPIHBP1-bound LPL.

55 The Q114P mutant bound LPL similarly to the N-terminal domain of GPIHBP1.

56 lished that chylomicronemia can be caused by LPL mutations that interfere with catalytic activity.

57 cases of chylomicronemia might be caused by LPL mutations that interfere with LPL's ability to bind

58 Hydrolysis of plasma triglycerides by LPL can be disrupted by the protein angiopoietin-like 4

59 d three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8,

60 eficiency had increased postprandial cardiac LPL activity and lower TAG levels only in the fed state.

61 eral PPARgamma target genes in 3T3-L1 cells (LPL, ORL1, and CEBPalpha) and PPARgamma-dependent adipog

62 2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL choleste

63 the frequencies of DP8alpha PBL and colonic LPL were lower in patients with IBD than in healthy dono

64 n the metabolic measures and used the common LPL(rs12678919) polymorphism to test for LPL-independent

65 rference in 3T3-L1 preadipocytes compromised LPL-dependent TG accumulation during the initial phase o

66 ction of these apolipoproteins and decreased LPL activity.

67 lts in multimerization of GPIHBP1, defective LPL binding, and severe hypertriglyceridemia.

68 and apoC-III inhibit lipolysis by displacing LPL from lipid emulsion particles.

69 Heparin dissociated LPL from the N-terminal domain, and partially from wild

70 complex with ANGPTL4, and upon dissociation, LPL regains lipase activity.

71 Strikingly, DP8alpha LPL and PBL exhibited a highly skewed repertoire toward

72 AT, likely via activation of AMPK, enhancing LPL activity and uptake of plasma triglyceride-derived f

73 wn-regulation of the mRNA level of aP2, FAS, LPL, HSL and PLIN1.

74 pression and lipid levels was discovered for LPL and C6orf184.

75 l-rich lipoproteins and is the co-factor for LPL as pressure increases.

76 cumstantial evidence suggests a function for LPL in either the formation or maintenance of integrin-a

77 conserved cysteines, that are important for LPL binding; nine of those were clustered in finger 2 of

78 y top cis-eSNPs were attenuated markedly for LPL, FADS2 and C6orf184, suggesting a shared genetic bas

79 tations with Alzheimer's disease, a role for LPL in learning and memory seems likely.

80 However, a role for LPL's N terminus has not been excluded, and published ev

81 mon LPL(rs12678919) polymorphism to test for LPL-independent effects.

82 n addition, through its "bridging function," LPL can mediate the acquisition of nascent chylomicrons

83 Furthermore, LPL that was bound to the N-terminal domain interacted w

84 Furthermore, LPL was required for the integrin-mediated enhancement o

85 Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluste

86 work conceptualizes a model for the GPIHBP1*LPL interaction based on biophysical measurements with h

87 , the time is ripe for new insights into how LPL-mediated lipoprotein metabolism in the brain impacts

88 We conclude that hypothalamic LPL functions in astrocytes to ensure appropriately bala

89 These results identify LPL as a key effector of Mst1 and establish a novel mech

90 We thus identify LPL as being key to alveolar macrophage development and

91 h Waldenstrom's macroglobulinemia or non-IgM LPL and in B cells from healthy donors and was absent or

92 Waldenstrom's macroglobulinemia and non-IgM LPL from B-cell disorders that have some of the same fea

93 Importantly, LPL treatment also induced an increase in RNA internaliz

94 roglobulinemia, a somatic variant (T-->C) in LPL cells was identified at position 38182641 at 3p22.2

95 icating that innate immunity is defective in LPL(-/-) mice.

96 efective marginal zone B cell development in LPL(-/-) mice.

97 motactic and adhesive cues, is diminished in LPL(-/-) B cells stimulated with chemokine.

98 LOX5AP, TNF, and KCNJ11 for main effects; in LPL and TUB for glycemic index interaction effects on wa

99 Common genetic variants found in LPL, APOA5, and GCKR are associated with triglycerides l

100 Despite the increase in LPL activity, the uptake of very low density lipoprotein

101 n WAT, abolishing a cold-induced increase in LPL activity.

102 Furthermore, expression of T89A LPL in LPL-deficient hematopoietic cells, using bone marrow chi

103 ulated in developing alveolar macrophages in LPL(-/-) pups, suggesting that precursor cells were not

104 pase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was a

105 ffspring may be due in part to reductions in LPL expression in skeletal muscle resulting in decreased

106 index, glucose, sex, rs328 and rs7007797 in LPL, rs662799 and rs3135506 in APOA5, and rs1260326 in G

107 ce of pneumococci from the alveolar space in LPL(-/-) mice was defective compared to that in Rag1(-/-

108 ylated p65(+) cells was markedly elevated in LPLs of chronically SIV-infected macaques compared with

109 de that ANGPTL4 can both bind and inactivate LPL complexed to GPIHBP1 and that inactivation of LPL by

110 4), and ANGPTL4 has been shown to inactivate LPL in vitro.

111 We also show that ANGPTL4-inactivated LPL was incapable of binding GPIHBP1.

112 Once inactivated, LPL dissociated from GPIHBP1.

113 We now show: (1) that ANGPTL4 inactivates LPL by catalyzing the unfolding of its hydrolase domain;

114 PTL4 was capable of binding and inactivating LPL complexed to GPIHBP1 on the surface of endothelial c

115 as capable of binding, but not inactivating, LPL at 4 degrees C, suggesting that binding alone was no

116 n of the fragmentation pattern of individual LPL class and optimization of all experimental condition

117 In liver and small intestine, CREB-H induces LPL coactivators, Apoa4, Apoa5, and Apoc2 that facilitat

118 is unlikely that apoC-I and apoC-III inhibit LPL via displacement of apoC-II from the lipoprotein sur

119 ipoprotein C-III (APOC3) is known to inhibit LPL, although there is also evidence that APOC3 increase

120 divalent cations for its ability to inhibit LPL.

121 We find that inhibited LPL is in a complex with ANGPTL4, and upon dissociation,

122 giopoietin-like protein 4 (ANGPTL4) inhibits LPL activity.

123 the lipasin-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulatin

124 ely, fasting induces Angptl4, which inhibits LPL in WAT to direct circulating TAG to cardiac and skel

125 Small intestinal LPLs had increased numbers of CD44(hi), CD62L(lo), KLRG1

126 uld elicit disease and provide insights into LPL sequences required for binding to GPIHBP1.

127 ny such mutation would provide insights into LPL sequences required for GPIHBP1 binding.

128 ole of APOC3 in triglyceride metabolism, its LPL independent action, and the complex and correlated n

129 recombinant human ANGPTL4 modified at a key LPL interacting site into nephrotic Buffalo Mna and Zuck

130 T cells lacking LPL do not form fully mature synapses and thus demonstra

131 on of LPL and does not depend on full-length LPL homodimers.

132 oth epithelial and lamina propria leukocyte (LPL) compartments.

133 Likewise, LPL was lower in carbonyl iron-fed rats compared to cont

134 h the APOA5, APOC1, BRAP, BUD13, CETP, LIPA, LPL, PLCG1, and ZPR1 genes.

135 ats due to reduced serum lipoprotein lipase (LPL) activity (3.1 vs. 5.0 mM/min; P=0.026).

136 4 inhibits extracellular lipoprotein lipase (LPL) activity and stimulates the lipolysis of triacylgly

137 III are known to inhibit lipoprotein lipase (LPL) activity, but the molecular mechanisms for this rem

138 or of GIP stimulation of lipoprotein lipase (LPL) activity, involving activation of protein kinase B

139 a protein that inhibits lipoprotein lipase (LPL) activity, is highly expressed in BAT.

140 etion and an increase in lipoprotein lipase (LPL) activity.

141 We also detect lipoprotein lipase (LPL) and apolipoprotein A5 (APOA5) harbouring specific A

142 to remnant particles by lipoprotein lipase (LPL) and their uptake by the liver.

143 II) is the co-factor for lipoprotein lipase (LPL) at the surface of triacylglycerol-rich lipoproteins

144 stigated in vivo whether lipoprotein lipase (LPL) facilitates the placental uptake of dietary retinyl

145 protein that transports lipoprotein lipase (LPL) from the subendothelial space to the luminal side o

146 protein that transports lipoprotein lipase (LPL) from the subendothelial spaces to the capillary lum

147 translated region of the lipoprotein lipase (LPL) gene.

148 ter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissu

149 whether lipid uptake via lipoprotein lipase (LPL) in astrocytes is required to centrally regulate ene

150 nd protein expression of lipoprotein lipase (LPL) in skeletal muscle was significantly decreased in t

151 Lipoprotein lipase (LPL) is a 448-amino-acid head-to-tail dimeric enzyme tha

152 Lipoprotein lipase (LPL) is rate limiting in the provision of triglyceride-r

153 diovascular disease, and lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of t

154 tion of HCV particles by lipoprotein lipase (LPL) reduces HCV infectivity and increases HCV binding t

155 ide metabolism, binds to lipoprotein lipase (LPL) through its N-terminal coiled-coil domain (ccd-Angp

156 molecule that transports lipoprotein lipase (LPL) to the capillary lumen, and discuss several newly s

157 Lipoprotein lipase (LPL) undergoes spontaneous inactivation via global unfol

158 d the association of the lipoprotein lipase (LPL) variant rs13702 with plasma lipids and explored its

159 or 1beta (PGC1beta), and lipoprotein lipase (LPL) were among the up-regulated genes identified.

160 thelial cells that binds lipoprotein lipase (LPL) within the interstitial space and shuttles it to th

161 endothelial cells, binds lipoprotein lipase (LPL) within the interstitial spaces and transports it ac

162 endogenous inhibitor of lipoprotein lipase (LPL), and it modulates lipid deposition and energy homeo

163 d-binding protein (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), hormone sensitive lipas

164 asma TGs in mice lacking lipoprotein lipase (LPL), hepatic heparan sulfate proteoglycan (HSPG) recept

165 ion, and relation to the lipoprotein lipase (LPL), however, remain elusive.

166 ceridemia, by inhibiting lipoprotein lipase (LPL)-mediated hydrolysis of plasma triglycerides to FFAs

167 f the bioavailability of lipoprotein lipase (LPL).

168 dependent on the enzyme lipoprotein lipase (LPL).

169 s due to a deficiency in lipoprotein lipase (LPL).

170 t stimulatory effects on lipoprotein lipase (LPL).

171 ng alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decrease

172 Using colonic lamina propria lymphocytes (LPL) and peripheral blood lymphocytes (PBL) from healthy

173 were elevated in lamina propria lymphocytes (LPLs).

174 e, IgM-secreting lymphoplasmacytic lymphoma (LPL).

175 comprehensive analysis of lysophospholipid (LPL) species based on shotgun lipidomics has not been es

176 ormed whole-genome sequencing of bone marrow LPL cells in 30 patients with Waldenstrom's macroglobuli

177 hat separating the FLD from the CCD-mediated LPL-inhibitory activity of full-length Angptl4 reveals l

178 ike in energy-dependent cells like myocytes, LPL is normally repressed in adult hepatocytes.

179 e) and pharmacological inhibition (P-407) of LPL by maintaining wild type and MCK-L0 mice on diets wi

180 vo studies showed that postnatal ablation of LPL in glial fibrillary acidic protein-expressing astroc

181 e study revealed significant accumulation of LPL species in the liver of ob/ob mice.

182 ase surface pressure and mimic the action of LPL.

183 ggest that apoC-II regulates the activity of LPL in a pressure-dependent manner.

184 exhibited elevated postprandial activity of LPL in the heart and skeletal muscle, but not in white a

185 ting that lipasin suppresses the activity of LPL specifically in cardiac and skeletal muscles.

186 L by ANGPTL4 greatly reduces the affinity of LPL for GPIHBP1.

187 Mice expressing a conditional allele of LPL (CD11c.Cre(pos)-LPL(fl/fl)) exhibited significant re

188 od was applied for comprehensive analysis of LPL species present in mouse liver samples.

189 r comprehensive and quantitative analysis of LPL species was developed.

190 Further analysis of LPL(-/-) mice will illuminate critical regulators of the

191 Thus, the binding of LPL to GPIHBP1 requires only the C-terminal portion of L

192 g with that finding, there was no binding of LPL to GPIHBP1-S107C in either cell-based or cell-free b

193 ceride-rich lipoproteins, prevent binding of LPL to the lipid/water interface.

194 ribed as an unfolding molecular chaperone of LPL that catalytically converts active LPL dimers into i

195 Mice with neuron-specific deletion of LPL have increases in food intake that lead to obesity,

196 I or apoC-III was needed for displacement of LPL from the lipid/water interface.

197 The regulatory N-terminal domain of LPL contains a consensus Mst1 phosphorylation site at Th

198 rotein metabolism, as well as the effects of LPL(rs12678919).

199 ision energy, and recovery and enrichment of LPL classes from the aqueous phase after solvent extract

200 An absence of GPIHBP1 prevents the entry of LPL into capillaries, blocking LPL-mediated triglyceride

201 y role of the top GWAS SNP for expression of LPL, FADS2 and C6orf184.

202 ctivator PPARGC1B, and reduced expression of LPL.

203 uring conditions, the C-terminal fragment of LPL refolds and binds GPIHBP1 avidly.

204 lucidation of the regulation and function of LPL in T-cell biology may illuminate new pathways for cl

205 ently with LPL and that the functionality of LPL depends on its localization on GPIHBP1.

206 omplexed to GPIHBP1 and that inactivation of LPL by ANGPTL4 greatly reduces the affinity of LPL for G

207 that fatty acids reduce the inactivation of LPL by Angptl4.

208 proteins in the irreversible inactivation of LPL by factors such as angptl4.

209 ion particles and consequently inhibition of LPL activity.

210 as a reversible, noncompetitive inhibitor of LPL.

211 cal relevance of the inherent instability of LPL, and sheds light on the molecular defects in a clini

212 Unlike the interaction of LPL with the Ly6 domain, the interaction of LPL with the

213 LPL with the Ly6 domain, the interaction of LPL with the N-terminal domain was significantly weakene

214 ifferent roles in regulating the kinetics of LPL binding.

215 All three homozygotes had very low levels of LPL in the preheparin plasma.

216 te the bundling activity and localization of LPL following T-cell receptor and chemokine receptor eng

217 ting Thr(89) to Ala impaired localization of LPL to the actin-rich lamellipodia of T cells.

218 Reduction or loss of LPL expression also reduces the velocity of T cells and

219 9A LPL mutant failed to restore migration of LPL-deficient T cells in vitro.

220 HBP1 requires only the C-terminal portion of LPL and does not depend on full-length LPL homodimers.

221 1, suggesting that the C-terminal portion of LPL is important for GPIHBP1 binding.

222 idates the molecular basis for regulation of LPL activity by ANGPTL4, highlights the physiological re

223 that appear important for the regulation of LPL activity.

224 02 induces the allele-specific regulation of LPL by miR-410 in humans.

225 port the role of APOC3 as a key regulator of LPL-independent pathways of triglyceride metabolism.

226 This triggers release of LPL from lipoproteins.

227 Recent evidence implicates a role of LPL in the brain in two processes: (a) the regulation of

228 Consistent with the essential role of LPL in triglyceride clearance, CREB-H-deficient mice sho

229 d metabolism and for elucidating the role of LPL species in signal transduction and other biological

230 The increased susceptibility of LPL(-/-) mice to pulmonary pneumococcal challenge correl

231 tivity by mitigating the global unfolding of LPL's catalytic domain.

232 ess efficient in catalyzing the unfolding of LPL; and (2) that its Glu-to-Lys substitution destabiliz

233 these PCs modulates its inhibitory effect on LPL activity.

234 verely diminished their protective effect on LPL and rendered the enzyme more susceptible to inactiva

235 4 cleavage reduces its inhibitory effects on LPL activity and decreases its ability to raise plasma t

236 Thr(89) We found that Mst1 can phosphorylate LPL in vitro and that Mst1 can interact with LPL in cell

237 Western blot analysis showed that placental LPL acts in concert with LDL receptor and LRP1.

238 nt for the actin-bundling protein L-plastin (LPL) have phenotypes similar to mice lacking Mst1, inclu

239 nt for the actin-bundling protein L-plastin (LPL) in B cell motility toward the chemokines CXCL12 and

240 w that the actin-bundling protein L-plastin (LPL) is required for the perinatal development of alveol

241 -specific, actin-bundling protein L-plastin (LPL) succumb rapidly to intratracheal pneumococcal infec

242 -specific, actin-bundling protein L-plastin (LPL).

243 a conditional allele of LPL (CD11c.Cre(pos)-LPL(fl/fl)) exhibited significant reductions in alveolar

244 with a novel strategy of sample preparation, LPL species present in biological samples can be determi

245 echanisms by which GPIHBP1 mutations prevent LPL binding and lead to chylomicronemia.

246 ymphocytes in the intestinal lamina propria (LPL) and cervical lymph nodes (CLN).

247 esidue that is located close to the putative LPL-binding region.

248 tion of iron to serum ex vivo or recombinant LPL in vitro decreased enzymatic activity in a dose-depe

249 hat are potentially important for regulating LPL activity.

250 missense mutations, G409R and E410V, render LPL susceptible to cleavage at residue 297 (a known furi

251 domain; (2) that binding to GPIHBP1 renders LPL largely refractory to this inhibition; and (3) that

252 -29a as the miRNA responsible for repressing LPL in hepatocytes, and found that decreasing hepatic mi

253 regeneration following irradiation required LPL.

254 of alveolar macrophage development requiring LPL.

255 ) adipocytes, but resistin treatment rescued LPL responsiveness to GIP.

256 ic variant, rs12721054/APOC1, and rs10096633/LPL are associated with >/=3 MetS components.

257 that rs174545 (FADS1:miR-181a-2), rs1059611 (LPL:miR-136), rs13702 (LPL:miR-410), rs1046875 (FN3KRP:m

258 R-181a-2), rs1059611 (LPL:miR-136), rs13702 (LPL:miR-410), rs1046875 (FN3KRP:miR-34a), rs7956 (MKRN2:

259 nd in 3 of 3 patients with non-IgM-secreting LPL (91% of all patients with LPL).

260 l receptor and chemokine receptor signaling, LPL is critical to the later stages of synapse maturatio

261 Triglyceride-rich lipoproteins stabilize LPL and protect the enzyme from inactivating factors suc

262 Importantly, the acidic domain stabilizes LPL catalytic activity by mitigating the global unfoldin

263 he activity of alemtuzumab in 28 symptomatic LPL (27 IgM and 1 IgA) patients.

264 Furthermore, expression of T89A LPL in LPL-deficient hematopoietic cells, using bone mar

265 Expression of the T89A LPL mutant failed to restore migration of LPL-deficient

266 isms in 1 glucose and 4 lipids loci (TCF7L2, LPL, APOA5, CETP, and APOC1/APOE/TOMM40) significantly a

267 We found that LPL supports 2 actin-based processes essential for corre

268 We show that LPL inactivation by this regulatable variant of ANGPTL4

269 Furthermore, we show that LPL knockdown in muscle cells decreased mitochondrial co

270 Here, we show that LPL's C-terminal domain is sufficient for GPIHBP1 bindin

271 hypothalamus-derived astrocytes showed that LPL expression is upregulated by oleic acid, whereas it

272 These results suggest that LPL may participate in signaling that enables lymphocyte

273 The LPL*GPIHBP1 complex is responsible for margination of tr

274 310) subunit of NF-kappaB exclusively in the LPL compartment.

275 In the presence of the LPL activator protein apoC-II, more of apoC-I or apoC-II

276 y predictable by the action of APOC3 through LPL.

277 e, suggesting that increasing adipose tissue LPL improves glucose metabolism in diet-induced obesity

278 NGPTL4 both bound with similar affinities to LPL, the N-terminal fragment was more potent in inactiva

279 GPIHBP1 is responsible for trafficking LPL across capillary endothelial cells and anchors LPL t

280 the ability of GPIHBP1 to bind and transport LPL.

281 roteins also lacked the ability to transport LPL from the basolateral to the apical surface of endoth

282 fied GPIHBP1 as the molecule that transports LPL to the capillary lumen, and have also identified oth

283 Here, we report that two LPL missense mutations initially identified in patients

284 We found, serendipitously, that two LPL missense mutations, G409R and E410V, render LPL susc

285 However, in vivo LPL is often complexed to glycosylphosphatidylinositol-a

286 When LPL was in complex with the acidic peptide corresponding

287 e from 4.84x10(-4) to 4.62x10(-18)), whereas LPL, TRIB1, ABCA1, APOA1-C3-A4-A5, CETP, and APOE displa

288 domain interacted with lipoproteins, whereas LPL bound to the Ly6 domain did not.

289 l lethality by somatic gene transfer wherein LPL in the brain remains absent, altered cognition ensue

290 We therefore asked whether LPL functions downstream of Mst1.

291 ther, these data define a mechanism by which LPL mutations could elicit disease and provide insights

292 nvestigated the interactions of ANGPTL4 with LPL-GPIHBP1 complexes on the surface of endothelial cell

293 mains of GPIHBP1 interact independently with LPL and that the functionality of LPL depends on its loc

294 in and the central Ly6 domain, interact with LPL as two distinct binding sites.

295 LPL in vitro and that Mst1 can interact with LPL in cells.

296 How ANGPTL4 interacts with LPL in this context is not known.

297 IHBP1 missense mutations that interfere with LPL binding cause familial chylomicronemia.

298 caused by LPL mutations that interfere with LPL's ability to bind to GPIHBP1.

299 to bind to GPIHBP1 without interfering with LPL catalytic activity or binding to heparin.

300 In other mice with LPL deficiency rescued from neonatal lethality by somati

301 -IgM-secreting LPL (91% of all patients with LPL).

302 les from an expanded cohort of patients with LPL, those with other B-cell disorders that have some of