ライフサイエンスコーパス: reelin

1 labeled for calbindin, calretinin, NeuN, and reelin.

2 tical circuits by secreting the glycoprotein reelin.

3 abrogated the decrease in VLDLRs induced by Reelin.

4 roteolytic processing of endothelium-derived Reelin.

5 mation was the extracellular matrix molecule reelin.

6 rocessed for immunostaining of calbindin and reelin.

7 rogliaform subtype, express the glycoprotein Reelin.

8 egulated by the extracellular matrix protein Reelin.

9 man astrocyte cell culture model to identify reelin, a factor intimately involved in the development

10 Initial studies found that loss of Reelin, a large, secreted glycoprotein encoded by the Re

11 sticity and NMDA receptor phosphorylation by Reelin, a regulator of brain development and modulator o

12 Moreover, Reelin, a secreted protein regulating neuronal positioni

13 n the marginal zone, and their expression of reelin, a signal that controls spatial ordering of corti

14 cortices that lack the secreted glycoprotein Reelin, a subset of neurons completed migration but then

15 Whereas overexpression of Reelin accelerated dendritic maturation, inactivation of

16 report that the extracellular matrix protein Reelin, acting through its downstream, intracellular Dab

17 The specificity of Reelin action on spontaneous neurotransmitter release is

18 cts may be at least partially independent of Reelin actions on hippocampal neurogenesis.

19 We propose a multistep mechanism in which Reelin activates Rap1, Rap1 upregulates NCad, and NCad i

20 Reelin signaling, but it is unclear whether Reelin acts directly on migrating SN-mDA neurons and how

21 ed in cortical interneurons: Reln coding for reelin; Adamts8 and Adamts15 belonging to the class of m

22 of CLASP2 regulates its interaction with the Reelin adaptor Dab1 and this association is required for

23 Reelin affects multiple pathways including through the r

24 Here, we show that Reelin also acts presynaptically, resulting in robust ra

25 Here, we identify Reelin, an extracellular matrix glycoprotein previously

26 Reelin, an extracellular matrix molecule, regulates neur

27 els of the extracellular matrix glycoprotein Reelin and activation of its downstream pathway resultin

28 Using reelin and apoE as ligands, we studied the impact of VLD

29 l in which activation of VLDLR and apoER2 by reelin and apoE induces ABCA1 expression and cholesterol

30 In addition, both reelin and apoE3 significantly increased phosphorylated

31 Reelin and apolipoprotein E (apoE), ligands of apoE rece

32 In vivo, Reelin and Dab1 are required for the normal extension of

33 bind to extracellular glycoproteins, such as Reelin and F-spondin, which leads to phosphorylation of

34 The FAK-Src complex, activated by upstream reelin and integrin beta1, can initiate a cascade of pho

35 -R2 and N-R6 bind to L1 and that full-length Reelin and its N-terminal fragment N-R6 proteolytically

36 Here, we report that full-length Reelin and its N-terminal fragments N-R2 and N-R6 bind t

37 We also show that Reelin and LGI1 co-localize in a subset of rat brain neu

38 sub-layer (L2a) that are immunoreactive for reelin and project to the dentate gyrus [17, 18].

39 At E15.5, expression of reelin and VLDLR was similar but expression of apolipopr

40 SPNs in reeler (which lacks reelin), and in mice deficient in components of the reel

41 We propose a model in which Abeta, Reelin, and ApoE receptors modulate neurotransmission an

42 e promoters (glutamic acid decarboxylase 67, Reelin, and brain-derived neurotrophic factor), leading

43 cts of normal and reeler mutant mice lacking Reelin, and from cell-free extracts containing normal or

44 entral spinal cord; the only areas devoid of Reelin are areas occupied by SPN or somatic motor neuron

45 hanisms that mediate postnatal activities of Reelin are not well understood.

46 We identified the glycoprotein reelin as a potentially useful marker, because it is exp

47 N-Cadherin interaction in vivo and identify Reelin as an extracellular upstream regulator and Erk1/2

48 e that the direct interaction between L1 and Reelin as well as the Reelin-mediated generation of L1-8

49 2, a dual function receptor for ApoE and for Reelin, as well as NMDA and AMPA receptors by sequestrat

50 s pathway could be used as murine models for Reelin-associated vocal deficits in humans.

51 ate that LXR activation results in decreased Reelin binding to VLDLR and reduced Dab1 phosphorylation

52 Extracellular Reelin binds to cell surface receptors and activates pho

53 estration of extracellular reelin with CR-50 reelin-blocking antibodies suppressed the increase in mi

54 5-beta bound to specific promoter regions of reelin, brain-derived neurotrophic factor (BDNF), and gl

55 ed the rescue of the behavioral phenotype by Reelin but did completely block the effects of Reelin on

56 y the dimeric ligands Fc-RAP, F-spondin, and Reelin but relatively weak clustering with the ligand ap

57 Dab1 is required for most effects of Reelin, but Dab1-independent pathways may contribute.

58 containing the extracellular matrix protein Reelin, but not control medium, further increased the ve

59 hatic endothelial cells in turn responded to Reelin by up-regulating monocyte chemotactic protein 1 (

60 At high concentrations of Abeta peptides, Reelin can no longer overcome the Abeta induced function

61 oreover, our data reveal a novel role of the Reelin cascade in adult brain function with potential im

62 Activation of the Reelin cascade leads to phosphorylation of Disabled-1, a

63 Deficiency in Reelin causes the forming dendrite to avoid its normal t

64 Reelin+ cells showed no staining in the striatum besides

65 Reelin choreographs neuronal migration to establish lami

66 we identified Dgcr2 as a novel member of the Reelin complex, regulating the phosphorylation of Reelin

67 Kdm5b depletion increased extracellular reelin concentration in the culture medium and increased

68 ndrial damage/autophagy; diminished neuronal reelin content (males); induction of Nurr1 and Pitx3 wit

69 not clear whether the secreted glycoprotein Reelin controls migration and dendritic growth as relate

70 However, little is known about how Reelin controls the cytoskeleton during neuronal migrati

71 Furthermore, loss of Reelin correlates with decreased survival of lung and br

72 Our findings suggest that reelin could be a previously unknown factor involved in

73 This demonstrates that the balance between Reelin-Dab1 signaling and LKB1-Stk25-GM130 regulates Gol

74 nclusively demonstrate an important role for Reelin-Dab1 signaling in the adult forebrain, and unders

75 ful to study the biological functions of the Reelin-Dab1 signaling pathway both in vitro and in vivo.

76 The Reelin-Dab1 signaling pathway regulates development of t

77 We find that Stk25, a modifier of Reelin-Dab1 signaling, regulates Golgi morphology and ne

78 Knock-out of APP or Reelin decreased dendritic arborization in cortical neur

79 In contrast, Reelin decreased VLDLRs, which was accompanied by an inc

80 xamine the cytoarchitectural consequences of Reelin deficiency, using high-throughput histology and n

81 Reelin-deficient (Reeler) mice exhibited impaired respon

82 Reelin-deficient mice showed abnormal collecting lymphat

83 , albeit less severe than, those observed in Reelin-deficient or VLDLR/ ApoER2 double-KO mice.

84 ficient mice partially overlap with those of Reelin-deficient reeler mice.

85 Therefore, this study links Reelin-dependent dendritogenesis with migration arrest a

86 s of early corticogenesis possibly through a Reelin-dependent mechanism.

87 is coincides with a complete blockade of the Reelin-dependent phosphorylation of NR2 subunits.

88 n complex, regulating the phosphorylation of Reelin-dependent substrates and the expression of Reelin

89 n-dependent substrates and the expression of Reelin-dependent transcriptional targets.

90 f SPN through electroporation of full-length Reelin DNA stopped SPN migration toward their destinatio

91 ved among distinct subtypes of somatostatin+/Reelin+ double-positive cells, including Hpse+ layer IV

92 Induction of the Reelin/E-cadherin axis is also observed in Kras mutant l

93 our data reveal that CLASP2 is an essential Reelin effector orchestrating cytoskeleton dynamics duri

94 gulates cell movement, and both X11alpha and Reelin enhance this effect.

95 are fundamental to the proper integration of Reelin-expressing interneurons into nascent cortical cir

96 early development, superficially positioned Reelin-expressing neurogliaform interneurons in the mous

97 By measuring reelin expression and promoter methylation status in 39

98 Here we analyzed reelin expression by immunohistochemistry in 17 normal b

99 developing DG, perhaps in part by affecting Reelin expression in a key compartment directly above th

100 dorsomedial cortex, and ventral expansion of Reelin expression in the cortical plate of the frontal c

101 of heterozygous reeler mice (HRM), in which reelin expression is down-regulated by approximately 50%

102 er decitabine treatment, we established that reelin expression levels correlated inversely with promo

103 The spatiotemporal pattern of Reelin expression, along with the inhibition of SPN migr

104 is a marked decrease ( approximately 50%) of reelin expression.

105 sition can change with location and level of reelin expression.

106 sed neurite outgrowth in vitro and prevented Reelin from increasing neurite outgrowth.

107 Thus, we define the cellular mechanism of reelin function during radial migration, elucidate the m

108 Loss of Reelin function results in the severe developmental diso

109 migration by exogenous Reelin, suggests that Reelin functions as a barrier to SPN migration during no

110 Therefore, Reelin functions as part of a polarity signaling system

111 Reelin ibsVRG neurons were larger (27.1 +/- 3.8 mum in d

112 This finding suggests that lack of reelin impairs GABAergic Purkinje neuron expression and/

113 ity against the extracellular matrix protein Reelin in a region directly above the developing LSB is

114 n promoter, we examined here the function of Reelin in control of sympathetic preganglionic neurons (

115 R and Dab1, that mediates other functions of Reelin in early brain development.

116 hese phenotypes are suggestive of a role for reelin in spatial patterning or structural organization

117 However, unlike reeler, levels of reelin in the C3G(gt)/(gt) spinal cord are normal, and D

118 The present study examined the effects of Reelin in the migration of sympathetic preganglionic neu

119 Ectopic expression of Reelin in the pathway of SPN through electroporation of

120 uronal maturation and synaptic plasticity by Reelin in the postnatal and adult brain.

121 Only when the expression level of ectopic reelin in the ventricular zone became very weak (E18.5)

122 Reelin in turn mediates inhibitory signals to migrating

123 decreased migration in response to exogenous reelin in vitro, a response that required Dab1.

124 s, these observations 1) solidify a role for Reelin in vocal communication of multiple species, 2) po

125 Reelin increased cell surface levels of APP and decrease

126 ha3beta1 integrin antibody prevented APP and Reelin-induced neurite outgrowth.

127 Reelin-induced tyrosine phosphorylation is responsible f

128 dentate gyrus subgranular zone, and a single-Reelin infusion increased the number but not complexity

129 s demonstrate that a single intrahippocampal Reelin infusion into the dorsal hippocampus has fast-act

130 fects of repeated or single intrahippocampal Reelin infusions on measures of depressive-like behavior

131 omplexity of newborn neurons, while repeated Reelin infusions restored both.

132 ts were reversed by both repeated and single-Reelin infusions.

133 These findings demonstrate that Reelin interacts with APP, potentially having important

134 d aberrant neurogenesis with preservation of reelin + interneurons, lowered concentration of oxidativ

135 Reelin is a glycoprotein that is critical for proper lay

136 Reelin is a neuromodulator that increases glutamatergic

137 Reelin is a secreted, signaling protein associated with

138 We suggest that reelin is a useful molecular marker for pre-BotC neurons

139 Reelin is able to rescue the deficits in AMPA, NMDA, GAB

140 Reelin is an extracellular matrix protein synthesized in

141 Reelin is an extracellular matrix protein that is vital

142 Reelin is an extracellular protein essential for neurona

143 Reelin is an extracellular protein that controls many as

144 The secreted glycoprotein Reelin is an important factor directing neuronal migrati

145 Together, these data reveal that reelin is essential for the targeting of LGN subnuclei b

146 During secondary migration, abundant Reelin is found in large areas of the ventral spinal cor

147 Reelin is known to activate signalling cascades regulati

148 uggest that in the subventricular zone where Reelin is not present but ApoER2, VLDLR, and Dab1, clust

149 In vivo, Reelin levels were increased in brains of APP knock-out

150 The Reelin ligand regulates a Dab1-dependent signaling pathw

151 g of clusterin to these receptors triggers a Reelin-like signal in cells expressing disabled-1 (Dab1)

152 The regulation of VLDLR by BDNF and Reelin may affect the migration of neurons and contribut

153 We conclude that reelin may play an important role in controlling invasiv

154 n, which suggests an autocrine mechanism for Reelin-mediated control of endothelial factor expression

155 raction between L1 and Reelin as well as the Reelin-mediated generation of L1-80 contribute to brain

156 Reelin-mediated generation of L1-80 is involved in neuri

157 pectedly, we discovered that the full-length Reelin moiety, but not the central fragment, is capable

158 tion status, whereas demethylation increased reelin mRNA expression in vitro.

159 Pre-BotC reelin neurons coexpress NK1R and Sst.

160 his suggests a compensatory mechanism, where reelin neurons trend to compensate for the loss of calbi

161 Reelin neurons were also found in the parahypoglossal an

162 elin but did completely block the effects of Reelin on hippocampal neurogenesis.

163 Possible functions of Reelin on SPN migration are discussed.

164 Deletion in mouse of either reelin or Dab1 induced alterations in the development of

165 Treatment of these mouse macrophages with reelin or human apoE3 significantly increased ABCA1 mRNA

166 wborn progeny, is eliminated in mice lacking REELIN or upon clonal depletion of DISABLED-1, which com

167 derived cortical interneurons express either Reelin or vasoactive intestinal polypeptide.

168 calcium-binding protein 1, cholecystokinin, reelin, or a combination of these molecules.

169 Mice that are deficient in Dab1, Reelin, or the Reelin receptors ApoER2 and VLDLR exhibit

170 This reelin- or apoER2-mediated up-regulation of ABCA1 expres

171 Reelin overexpression in MDA-MB231 cells, as well as inc

172 ound mutants carrying mutations in both, the Reelin pathway and Lis1 exhibit hydrocephalus, a phenoty

173 We previously showed that the Reelin pathway and the Pafah1b complex interact genetica

174 Components of the Reelin pathway are highly expressed during development,

175 a cell-autonomous and critical role for the Reelin pathway in regulating dendritic development and t

176 nd loss-of-function studies to show that the Reelin pathway regulates migration and dendritic develop

177 t interacts with Dab1, a key mediator of the Reelin pathway that controls several aspects of brain de

178 isabled-1 is a key signaling molecule in the Reelin pathway that plays a critical role in neuronal mi

179 how that Dab1, an essential component of the reelin pathway, is required in radially migrating neuron

180 ent decrease in Dab1, a key component of the Reelin pathway, is sufficient to induce behavioral defic

181 Here we demonstrate that the Reelin pathway, which determines the development of laye

182 dent on Dab1, a key signaling protein in the Reelin pathway.

183 xon junction array search for Nova-dependent reelin-pathway RNAs at E14.5 revealed only one candidate

184 cule L1 and the extracellular matrix protein Reelin play crucial roles in the developing nervous syst

185 early deficits of somatostatin-positive and Reelin-positive interneurons in both Htt subpallial null

186 -cells in layer-2 emerged around birth while reelin-positive stellate-cells were scattered throughout

187 re caudally (>12.8 mm caudal to Bregma) than reelin pre-BotC neurons (15.5 +/- 2.4 mum in diameter, <

188 ls of histone H2B monoubiquitination, at the reelin promoter.

189 Reelin promotes laterally-biased movements in mDA neuron

190 et out to express and purify the full length Reelin protein and a biologically active central fragmen

191 Loss of reelin protein expression correlated significantly with

192 Reelin protein is expressed in a complementary pattern,

193 Application of Reelin protein to reeler cortices destabilized tangentia

194 uction mechanisms elicited by these purified Reelin proteins in cortical neurons.

195 we demonstrate in mice that for CGE-derived reelin (Re)-positive and calretinin (Cr)-positive (but n

196 w here that BDNF increased the levels of the Reelin receptor (VLDL receptor (VLDLR)) in hippocampal n

197 catalytic subunit of Pafah1b also binds the Reelin receptor VLDLR.

198 of apolipoprotein E receptor 2 (ApoER2) (the reelin receptor) was much lower in LXRbeta(-/-) than in

199 Mice deficient in another Reelin receptor, very low-density lipoprotein receptor (

200 e that are deficient in Dab1, Reelin, or the Reelin receptors ApoER2 and VLDLR exhibit severely pertu

201 components of the reelin signaling pathway (reelin receptors VldlR and ApoER2, the cytoplasmic adapt

202 ITSN1 genetically interacts with Reelin receptors, as evidenced by the prominent neuronal

203 , triggers activation of this cohort of LRP8-Reelin-regulated neuronal (LRN) enhancers that serve as

204 bition and rescue experiments indicated that Reelin regulates migration through Rap1 and Akt, and tha

205 We discovered that Reelin regulates several phosphorylation sites within th

206 RGC axons in mutant mice lacking functional reelin (reln(rl/rl)) revealed reduced patterns of vLGN a

207 cretome identified the extracellular protein reelin (RELN) as a key component of this process.

208 ession of the gene encoding the glycoprotein reelin (Reln) in Chd7-deficient GCps.

209 rt the identification of causal mutations in reelin (RELN) in seven ADLTE-affected families without L

210 We establish that the synaptic modulator reelin (RELN) is a critical mediator of this vulnerabili

211 We discovered a hypomorphic reelin (Reln) mutant with abnormal cortical lamination a

212 layering requires an extracellular protein, Reelin (Reln), an intracellular signaling molecule, Disa

213 dm5b depletion, notably the up-regulation of reelin (Reln), the inhibition of steroid biosynthetic pa

214 g glutamic acid decarboxylase 67 (GAD67) and reelin (RELN).

215 This effect of Reelin requires a modest but significant increase in pre

216 ing downstream AKT signaling or inactivating reelin restored migration.

217 reeler mutant mouse, the lack of the protein Reelin results in cell-type and region-dependent changes

218 In contrast, intensity of reelin (RLN) expression was significantly increased in a

219 was a significant increase in the number of reelin-secreting neurons in layers II and III generated

220 y for binding Disabled-1 and transducing the Reelin signal, was also necessary for development of the

221 euroblasts, which could be linked to reduced reelin signaling and disorganized radial glial cell fibe

222 on is spatiotemporally regulated to modulate Reelin signaling and ensure normal neuron positioning in

223 to highlight the most fundamental aspects of Reelin signaling and integrate how these various neuromo

224 f Dab1 to mediate neuronal responsiveness to reelin signaling and neuronal migration, suggesting new

225 er, it is not known whether a dysfunction in Reelin signaling during perinatal stages increases the r

226 ic mouse and retroviral reporters along with Reelin signaling gain-of-function and loss-of-function s

227 By specifically inactivating Reelin signaling in mDA neurons we demonstrate its direc

228 The interplay between BDNF and Reelin signaling in neurodevelopment is not fully unders

229 tor (GPCR) signaling pathway, axon guidance, reelin signaling in neurons, and ERK/MAPK signaling.

230 A recent paper uncovers a new function for Reelin signaling in specifying dendritic compartmentaliz

231 In the years since, the known functions of Reelin signaling in the brain have expanded to include m

232 These observations highlight a role for reelin signaling in the directed migration of mammary ep

233 increasing body of evidence to suggest that Reelin signaling is a critical player in the modulation

234 These results uncover a mechanism by which Reelin signaling is activated by communication between t

235 SIGNIFICANCE STATEMENT: Reelin signaling is important for brain development and

236 Reelin signaling is required for appropriate cell migrat

237 We find that Reelin signaling is required for the striking enrichment

238 fat pad and provide the first evidence that reelin signaling may be crucial for regulating the migra

239 , and in mice deficient in components of the reelin signaling pathway (reelin receptors VldlR and Apo

240 tify nectins and afadin as components of the reelin signaling pathway and demonstrate that coincidenc

241 The Reelin signaling pathway controls radial neuronal migrat

242 g cerebral cortex, but that mutations in the Reelin signaling pathway do not affect its expression.

243 er mice and subsequent identification of the Reelin signaling pathway have strongly informed models o

244 and suggest that C3G acts downstream in the reelin signaling pathway in control of SPN migration.

245 that binds CrkL, could act downstream in the reelin signaling pathway in control of SPN migration.

246 These findings suggest a central AKT-FOXG1-reelin signaling pathway in FMCD and support pathway inh

247 The Reelin signaling pathway plays a crucial role in regulat

248 ed dendritic maturation, inactivation of the Reelin signaling pathway specifically in adult neuroprog

249 protein that is an obligate effector of the Reelin signaling pathway, and is critical for neuronal m

250 CLASP2 as a key cytoskeletal effector in the Reelin signaling pathway.

251 increased phosphorylation of the downstream reelin signaling target Disabled-1 (Dab1).

252 these data identify ITSN1 as a component of Reelin signaling that acts predominantly by facilitating

253 Furthermore, reelin signaling to Rap1 promotes neuronal Cdh2 function

254 mber of key target genes with known roles in Reelin signaling, a critical regulator of neuronal migra

255 n of SN-mDA neurons is altered in absence of Reelin signaling, but it is unclear whether Reelin acts

256 lar adaptor protein activated in response to reelin signaling, is expressed in the developing mammary

257 Reelin signaling, which is mediated in part by a key ada

258 crease the risk of behavioral deficits alter Reelin signaling.

259 ons(SPNs) in the spinal cord is regulated by reelin signaling.

260 Disabled-1, an adaptor protein required for Reelin signaling.

261 n unexpected functional link between LXR and Reelin signaling.

262 and is involved in brain development through Reelin signaling.

263 nstream signaling adaptor Dab1 to facilitate Reelin signaling.

264 gene encoding VLDLR, a receptor important in reelin signaling.

265 o psychiatric disorders linked to defects in Reelin signaling.

266 nes during memory formation, linking this to Reelin signaling.

267 and epigenetic changes in components of the Reelin-signaling pathway (RELN, DAB1) are associated wit

268 multiple species, 2) point to the canonical Reelin-signaling pathway as critical for development of

269 uction or absence of these components of the Reelin-signaling pathway.

270 Reelin signals via the lipoprotein receptors very low de

271 Reelin simultaneously regulates NMDA-receptor transmissi

272 In reeler, which lacks Reelin, SPN also undergo primary migration to the ventro

273 Reelin stimulation of cultured neurons induces the exten

274 to defective neuronal migration and ablates Reelin stimulation of hippocampal long-term potentiation

275 tions significantly decrease serum levels of Reelin, suggesting an inhibitory effect of mutations on

276 the inhibition of SPN migration by exogenous Reelin, suggests that Reelin functions as a barrier to S

277 ells, as well as incubation with recombinant reelin, suppressed cell migration, invadopodia formation

278 Here we show that Reelin, the Rap1 GTPase and N-cadherin (NCad) are import

279 Reelin thus plays a role in restraining RAS and PI3-kina

280 , thereby critically reducing the ability of Reelin to enhance synaptic glutamate receptor activity.

281 In the neocortex, CR cells secrete reelin to instruct the radial migration of projection ne

282 The binding of Reelin to its receptor, LRP8, triggers activation of thi

283 As a result, the ability of Reelin to prevent LTP suppression by extracts from AD-af

284 e deacetylase inhibitors, partially restored reelin transcription and promoted the accumulation of mu

285 lls, due at least in part to derepression of reelin transcription in a manner dependent on the forkhe

286 Similarly, Reelin treatment increased cell velocity in the presence

287 multiple axons, both of which are rescued by Reelin treatment.

288 Reln gene, encoding the extracellular ligand REELIN, uncovered NEUROD2 binding to conserved E-box ele

289 Using a transgenic mouse that expressed reelin under the nestin promoter, we examined here the f

290 Reelin was expressed in the luminal epithelium and myoep

291 ggregate near the central canal when ectopic reelin was expressed.

292 Recently, reelin was found to be epigenetically silenced in gastri

293 Although Reelin was identified more than a decade ago, its functi

294 cutaneous injections of CORT for 3 weeks and Reelin was infused through an inserted canula in the lef

295 sporter, GABA transaminase, parvalbumin, and reelin were all highly expressed in breast cancer metast

296 RELN encodes a secreted protein, Reelin, which has important functions in both the develo

297 Reelin, which is expressed in theca cells, triggers a si

298 g neural progenitors showed misexpression of reelin, which led to a non-cell autonomous migration def

299 lipoprotein receptor (Vldlr) and its ligand reelin, which unexpectedly regulate FGFR-dependent epith

300 However, the interaction of Reelin with adhesion molecules, such as L1, has remained

301 Sequestration of extracellular reelin with CR-50 reelin-blocking antibodies suppressed